Updated on 2025/06/19

写真a

 
YUHKI Koh-ichi
 
Organization
School of Medicine Medical Course Basic Medicine Pharmacology
Other name(s)
YUKI Koichi
External link

Degree

  • 博士(医学) ( 2004.6   旭川医科大学 )

  • 修士(医科学) ( 1997.3   筑波大学 )

Research Interests

  • Pharmacology

Research Areas

  • Life Science / Molecular biology

  • Life Science / Cardiology

  • Life Science / Pharmacology

  • Life Science / Urology

  • Life Science / Gastroenterology

Education

  • University of Tsukuba   Graduate School, Division of Medical Science

    - 1997.3

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    Country: Japan

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Research History

  • Hokkaido University

    2020.4 - 2024.9

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  • Nayoro City University

    2018.11 - 2024.9

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  • 北海道立旭川高等看護学院   看護学科   非常勤講師

    2012.10 - 2025.3

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  • Asahikawa Medical University   School of Medicine   Associate Professor

    2012

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  • University of Tsukuba

    2010.10 - 2016.3

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  • Asahikawa Medical University   School of Medicine   Lecturer

    2006 - 2012

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  • University of Tsukuba   Life Science Center of Tsukuba Advanced Research Alliance

    2000.7 - 2010.9

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  • Asahikawa Medical University   School of Medicine   Research Assistant

    2000 - 2006

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  • University of Tsukuba   Research Assistant

    1998.4 - 2000.5

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Professional Memberships

Papers

  • Prostaglandin E2 mediates the late phase of ischemic preconditioning in the heart via its receptor subtype EP4 Reviewed

    Kanno T., Nakagawa N., Aonuma T., Kawabe J., Yuhki K., Takehara N., Hasebe N., Ushikubi F.

    Heart and Vessels   38 ( 4 )   606 - 613   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00380-022-02219-4

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  • Facilitation of colonic T cell immune responses is associated with an exacerbation of dextran sodium sulfate–induced colitis in mice lacking microsomal prostaglandin E synthase-1 Reviewed

    Fumiaki Kojima, Hiroki Sekiya, Yuka Hioki, Hitoshi Kashiwagi, Makoto Kubo, Masaki Nakamura, Shotaro Maehana, Yoshitaka Imamichi, Koh-ichi Yuhki, Fumitaka Ushikubi, Hidero Kitasato, Takafumi Ichikawa

    Inflammation and Regeneration   42 ( 1 )   2022.12

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title><sec>
    <title>Background</title>
    Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that acts downstream of cyclooxygenase and plays a major role in inflammation by converting prostaglandin (PG) H<sub>2</sub> to PGE<sub>2</sub>. The present study investigated the effect of genetic deletion of mPGES-1 on the development of immunologic responses to experimental colitis induced by dextran sodium sulfate (DSS), a well-established model of inflammatory bowel disease (IBD).


    </sec><sec>
    <title>Methods</title>
    Colitis was induced in mice lacking mPGES-1 (mPGES-1<sup>−/−</sup> mice) and wild-type (WT) mice by administering DSS for 7 days. Colitis was assessed by body weight loss, diarrhea, fecal bleeding, and histological features. The colonic expression of mPGES-1 was determined by real-time PCR, western blotting, and immunohistochemistry. The impact of mPGES-1 deficiency on T cell immunity was determined by flow cytometry and T cell depletion <italic>in vivo</italic>.


    </sec><sec>
    <title>Results</title>
    After administration of DSS, mPGES-1<sup>−/−</sup> mice exhibited more severe weight loss, diarrhea, and fecal bleeding than WT mice. Histological analysis further showed significant exacerbation of colonic inflammation in mPGES-1<sup>−/−</sup> mice. In WT mice, the colonic expression of mPGES-1 was highly induced on both mRNA and protein levels and colonic PGE<sub>2</sub> increased significantly after DSS administration. Additionally, mPGES-1 protein was localized in the colonic mucosal epithelium and infiltrated inflammatory cells in underlying connective tissues and the lamina propria. The abnormalities consistent with colitis in mPGES-1<sup>−/−</sup> mice were associated with higher expression of colonic T-helper (Th)17 and Th1 cytokines, including interleukin 17A and interferon-γ. Furthermore, lack of mPGES-1 increased the numbers of Th17 and Th1 cells in the lamina propria mononuclear cells within the colon, even though the number of suppressive regulatory T cells also increased. CD4<sup>+</sup> T cell depletion effectively reduced symptoms of colitis as well as colonic expression of Th17 and Th1 cytokines in mPGES-1<sup>−/−</sup> mice, suggesting the requirement of CD4<sup>+</sup> T cells in the exacerbation of DSS-induced colitis under mPGES-1 deficiency.


    </sec><sec>
    <title>Conclusions</title>
    These results demonstrate that mPGES-1 is the main enzyme responsible for colonic PGE<sub>2</sub> production and deficiency of mPGES-1 facilitates the development of colitis by affecting the development of colonic T cell–mediated immunity. mPGES-1 might therefore impact both the intestinal inflammation and T cell–mediated immunity associated with IBD.


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    DOI: 10.1186/s41232-021-00188-1

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    Other Link: https://link.springer.com/article/10.1186/s41232-021-00188-1/fulltext.html

  • 卵巣におけるプロスタグランジンD2合成遺伝子の発現解析

    今道 力敬, 結城 幸一, 矢澤 隆志, 牛首 文隆

    日本内分泌学会雑誌   96 ( 1 )   340 - 340   2020.8

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    Language:Japanese   Publisher:(一社)日本内分泌学会  

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  • Prostaglandin F2α Facilitates Platelet Activation by Acting on Prostaglandin E2 Receptor Subtype EP3 and Thromboxane A2 Receptor TP in Mice Reviewed

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Yoshitaka Imamichi, Fumiaki Kojima, Shima Kumei, Yoshikazu Tasaki, Shuh Narumiya, Fumitaka Ushikubi

    Thrombosis and Haemostasis   119 ( 08 )   1311 - 1320   2019.8

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    Publishing type:Research paper (scientific journal)   Publisher:Georg Thieme Verlag KG  

    <title>Abstract</title>Platelets play an important role in both physiological hemostasis and pathological thrombosis. Thromboxane (TX) A2 and prostaglandin (PG) I2 are well known as a potent stimulator and an inhibitor of platelet function, respectively. Recently, PGE2 has also been reported to regulate platelet function via PGE2 receptor subtypes. However, the effect of PGF2α on platelet function remains to be determined. The aim of the present study was to clarify the effect of PGF2α on murine platelet function both in vitro and in vivo. Platelets prepared from wild-type mice (WT platelets) expressed several types of prostanoid receptors, including the PGE2 receptor subtype EP3 and the TXA2 receptor TP, while expression of the PGF2α receptor FP was not detected. In WT platelets, PGF2α potentiated adenosine diphosphate-induced aggregation in a concentration-dependent manner, while PGF2α alone did not induce aggregation. In platelets prepared from mice lacking FP, however, PGF2α-induced potentiation was not significantly different from that in WT platelets. Interestingly, the potentiation was significantly blunted in platelets lacking EP3 or TP and disappeared completely in platelets lacking both EP3 and TP. Accordingly, PGF2α decreased the cyclic adenosine monophosphate level via EP3 and increased the inositol triphosphate level via TP in WT platelets. Intravenously administered PGF2α significantly shortened the bleeding time and aggravated arachidonic acid-induced acute thromboembolism in WT mice, suggesting that PGF2α works as a platelet stimulator also in vivo. In conclusion, PGF2α potentiates platelet aggregation in vitro via EP3 and TP but not FP. Accordingly, PGF2α facilitates hemostasis and thromboembolism in vivo.

    DOI: 10.1055/s-0039-1688906

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  • Cyclooxygenase-2 is acutely induced by CCAAT/enhancer-binding protein β to produce prostaglandin E2 and F2α following gonadotropin stimulation in Leydig cells. Reviewed International journal

    Takashi Yazawa, Yoshitaka Imamichi, Koh-Ichi Yuhki, Junsuke Uwada, Daisuke Mikami, Masayuki Shimada, Kaoru Miyamoto, Takeshi Kitano, Satoru Takahashi, Toshio Sekiguchi, Nobuo Suzuki, Md Rafiqul Islam Khan, Fumitaka Ushikubi, Akihiro Umezawa, Takanobu Taniguchi

    Molecular reproduction and development   86 ( 7 )   786 - 797   2019.7

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    Cyclooxygenase 2 (COX-2) is an inducible rate-limiting enzyme for prostanoid production. Because COX-2 represents one of the inducible genes in mouse mesenchymal stem cells upon differentiation into Leydig cells, we investigated COX-2 expression and production of prostaglandin (PG) in Leydig cells. Although COX-2 was undetectable in mouse testis, it was transiently induced in Leydig cells by human chorionic gonadotropin (hCG) administration. Consistent with the finding that Leydig cells expressed aldo-keto reductase 1B7 (PGF synthase) and PGE synthase 2, induction of COX-2 by hCG caused a marked increase in testicular PGF 2α and PGE 2 levels. Using mouse Leydig cell tumor-derived MA-10 cells as a model, it was indicated by reporter assays and electron mobility shift assays that transcription of the COX-2 gene was activated by CCAAT/enhancer-binding protein β (C/EBPβ) with cAMP-stimulation. C/EBPβ expression was induced by cAMP-stimulation, whereas expression of C/EBP homolog protein (CHOP) was robustly downregulated. Transfection of CHOP expression plasmid inhibited cAMP-induced COX-2 promoter activity. In addition, CHOP reduced constitutive COX-2 expression in other mouse Leydig cell tumor-derived TM3 cells. These results indicate that COX-2 is induced in Leydig cells by activation of C/EBPβ via reduction of CHOP expression upon gonadotropin-stimulation to produce PGF 2α and PGE 2 .

    DOI: 10.1002/mrd.23163

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  • Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice Reviewed

    Shima Kumei, Koh-Ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Yoshitaka Imamichi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    FASEB Journal   32 ( 5 )   2354 - 2365   2018.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:FASEB  

    DOI: 10.1096/fj.201700590R

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  • Roles of prostanoids in the regulation of platelet function

    Kashiwagi H., Yuhki K., Imamichi Y., Kojima F., Kumei S., Narumiya S., Ushikubi F.

    Thrombosis & Haemostasis: Research   2 ( 2 )   1014   2018

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  • Diethylstilbestrol administration inhibits theca cell androgen and granulosa cell estrogen production in immature rat ovary Reviewed

    Yoshitaka Imamichi, Toshio Sekiguchi, Takeshi Kitano, Takashi Kajitani, Reiko Okada, Yoshihiko Inaoka, Kaoru Miyamoto, Junsuke Uwada, Satoru Takahashi, Takahiro Nemoto, Asuka Mano, Md Rafiqul Islam Khan, Md Tariqul Islam, Koh-ichi Yuhki, Hitoshi Kashiwagi, Fumitaka Ushikubi, Nobuo Suzuki, Takanobu Taniguchi, Takashi Yazawa

    SCIENTIFIC REPORTS   7   2017.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-017-08780-7

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  • Cigarette smoke extract inhibits platelet aggregation by suppressing cyclooxygenase activity Reviewed

    Kashiwagi H, Yuhki K, Imamichi Y, Kojima F, Kumei S, Higashi T, Horinouchi T, Miwa S, Narumiya S, Ushikubi F

    TH Open   1 ( 2 )   e122 - e129   2017

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Georg Thieme Verlag KG  

    <title>Abstract</title>The results of studies that were performed to determine whether cigarette smoking affects platelet function have been controversial, and the effects of nicotine- and tar-free cigarette smoke extract (CSE) on platelet function remain to be determined. The aim of this study was to determine the effect of CSE on platelet aggregation and to clarify the mechanism by which CSE affects platelet function. CSE inhibited murine platelet aggregation induced by 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619), a thromboxane (TX) A2 receptor agonist, and that induced by collagen with respective IC50 values of 1.05 ± 0.14% and 1.34 ± 0.19%. A similar inhibitory action of CSE was also observed in human platelets. CSE inhibited arachidonic acid–induced TXA2 production in murine platelets with an IC50 value of 7.32 ± 2.00%. Accordingly, the inhibitory effect of CSE on collagen-induced aggregation was significantly blunted in platelets lacking the TXA2 receptor compared with the inhibitory effect in control platelets. In contrast, the antiplatelet effects of CSE in platelets lacking each inhibitory prostanoid receptor, prostaglandin (PG) I2 receptor and PGE2 receptor subtypes EP2 and EP4, were not significantly different from the effects in respective control platelets. Among the enzymes responsible for TXA2 production in platelets, the activity of cyclooxygenase (COX)-1 was inhibited by CSE with an IC50 value of 1.07 ± 0.15% in an uncompetitive manner. In contrast, the activity of TX synthase was enhanced by CSE. The results indicate that CSE inhibits COX-1 activity and thereby decreases TXA2 production in platelets, leading to inhibition of platelet aggregation.

    DOI: 10.1055/s-0037-1607979

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  • Thromboxane A(2) is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions Reviewed

    Tsugunobu Andoh, Ai Yamamoto, Satomi Haza, Koh-ichi Yuhki, Fumitaka Ushikubi, Shu Narumiya, Yasushi Kuraishi

    ACTA DERMATO-VENEREOLOGICA   96 ( 7 )   899 - 904   2016.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.2340/00015555-2437

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  • 11-Ketotestosterone Is a Major Androgen Produced in Human Gonads Reviewed

    Yoshitaka Imamichi, Koh-ichi Yuhki, Makoto Orisaka, Takeshi Kitano, Kuniaki Mukai, Fumitaka Ushikubi, Takanobu Taniguchi, Akihiro Umezawa, Kaoru Miyamoto, Takashi Yazawa

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   101 ( 10 )   3582 - 3591   2016.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/jc.2016-2311

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  • The Novel Prostaglandin I2 Mimetic ONO-1301 Escapes Desensitization in an Antiplatelet Effect Due to Its Inhibitory Action on Thromboxane A(2) Synthesis in Mices Reviewed

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Osamu Takahata, Yoshiki Sakai, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   353 ( 2 )   269 - 278   2015.5

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    DOI: 10.1124/jpet.115.222612

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  • Prostacyclin stimulated integrin-dependent angiogenic effects of endothelial progenitor cells and mediated potent circulation recovery in ischemic hind limb model. Reviewed

    Aburakawa Y, Kawabe J, Okada M, Yamauchi A, Asanome A, Kabara M, Matsuki M, Takehara N, Nakagawa N, Okumura S, Minami Y, Mizukami Y, Yuhki K, Ushikubi F, Hasebe N

    Circulation journal : official journal of the Japanese Circulation Society   77 ( 4 )   1053 - 1062   2013

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    DOI: 10.1253/circj.CJ-12-0897

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  • 17 beta-Estradiol is critical for the preovulatory induction of prostaglandin E-2 synthesis in mice Reviewed

    Katsumi Toda, Masafumi Ono, Koh-ichi Yuhki, Fumitaka Ushikubi, Toshiji Saibara

    MOLECULAR AND CELLULAR ENDOCRINOLOGY   362 ( 1-2 )   176 - 182   2012.10

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    DOI: 10.1016/j.mce.2012.06.006

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  • The intrinsic prostaglandin E2-EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice. Reviewed

    Nakagawa N, Yuhki K, Kawabe J, Fujino T, Takahata O, Kabara M, Abe K, Kojima F, Kashiwagi H, Hasebe N, Kikuchi K, Sugimoto Y, Narumiya S, Ushikubi F

    Kidney international   82 ( 2 )   158 - 171   2012.7

  • プロスタグランジンE2(PGE2)のその受容体サブタイプEP4アゴニストの腎間質線維化抑制効果 in vitroでの検討

    鹿原 真樹, 中川 直樹, 松木 孝樹, 珍田 純子, 藤野 貴行, 結城 幸一, 牛首 文隆, 長谷部 直幸

    日本腎臓学会誌   54 ( 3 )   239 - 239   2012.4

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  • Roles of prostanoids in the pathogenesis of cardiovascular diseases: Novel insights from knockout mouse studies. Invited Reviewed

    Yuhki K., Kojima F., Kashiwagi H., Kawabe J., Fujino T., Narumiya S., Ushikubi F.

    Pharmacology and Therapeutics   129 ( 2 )   195 - 205   2011.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.pharmthera.2010.09.004

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  • Selective activation of the prostaglandin E-2 receptor subtype EP2 or EP4 leads to inhibition of platelet aggregation Reviewed

    Shuhko Kuriyama, Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Takehiro Yamada, Takayuki Fujino, Akiyoshi Hara, Koji Takayama, Takayuki Maruyama, Akitoshi Yoshida, Shuh Narumiya, Fumitaka Ushikubi

    THROMBOSIS AND HAEMOSTASIS   104 ( 4 )   796 - 803   2010.10

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    DOI: 10.1160/TH10-01-0043

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  • Roles of prostanoids in the pathogenesis of cardiovascular diseases. Invited Reviewed

    Yuhki K., Kashiwagi H., Kojima F., Kawabe J., Ushikubi F.

    International Angiology   29 ( suppl. 2 )   19 - 27   2010.4

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  • Prostaglandin I2 promotes recruitment of endothelial progenitor cells and limits vascular remodeling. Reviewed

    Kawabe J., Yuhki K., Okada M., Kanno T., Yamauchi A., Tashiro N., Sasaki T., Okumura S., Nakagawa N., Aburakawa Y., Takehara N., Fujino T., Hasebe N., Narumiya S., Ushikubi F.

    Arteriosclerosis, Thrombosis and Vascular Biology   30 ( 3 )   464 - 470   2010.2

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    DOI: 10.1161/ATVBAHA.109.193730

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  • Prostaglandin I2 plays a key role in zymosan-induced mouse pleurisy Reviewed

    Koh-ichi Yuhki, Fumitaka Ushikubi, Hiroaki Naraba, Akinori Ueno, Hirotsugu Kato, Fumiaki Kojima, Shuh Narumiya, Yukihiko Sugimoto, Misao Matsushita, Sachiko Oh-ishi

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   325 ( 2 )   601 - 609   2008.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1124/jpet.107.134494

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  • プロスタノイドの糖尿病性および腎摘出後腎症における役割 受容体欠損マウスを用いた検討

    藤野 貴行, 阿部 和利, 中川 直樹, 長谷部 直幸, 結城 幸一, 川辺 淳一, 菊池 健次郎, 牛首 文隆

    日本腎臓学会誌   49 ( 3 )   337 - 337   2007.4

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  • Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo. Reviewed

    Ueno M, Kakinuma Y, Yuhki K, Murakoshi N, Iemitsu M, Miyauchi T, Yamaguchi I

    Journal of pharmacological sciences   101 ( 2 )   151 - 158   2006.6

  • The role of the prostanoids in inflammatory tachycardia. Invited Reviewed

    Yuhki K., Kawabe J., Ushikubi F.

    American Journal of Physiology   290   R1751 - R1751   2006.4

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  • 【プロスタグランジンの多様性】循環器系におけるプロスタノイドの役割

    結城 幸一, 藤野 貴行, 川辺 淳一, 原 明義, 牛首 文隆

    炎症と免疫   14 ( 1 )   59 - 65   2005.12

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    Language:Japanese   Publisher:(株)先端医学社  

    PGとTXよりなるプロスタノイドは,生体内でさまざまな作用を発揮する生理活性脂質である.また,その作用はおのおののプロスタノイドに特異的なレセプターを介して発揮される.一方,循環器系の臓器や細胞には,多種類のプロスタノイドレセプターが広く発現している.さらに,循環器系で認められるさまざまな病態に伴い,プロスタノイド産生が亢進することが知られており,その循環器系での作用が注目されてきた.しかし,これらプロスタノイドの作用が生理的・病態生理的にどの程度重要な役割を果たすのかに関し,いまだ不明な点が多い(著者抄録)

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  • Fat, keeping the heart healthy? Invited Reviewed

    Yuhki K, Kawabe J, Ushikubi F

    NATURE MEDICINE   11 ( 10 )   1048 - 1049   2005.10

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    DOI: 10.1038/nm1005-1048

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  • Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor Reviewed

    Hara A, Yuhki K, Fujino T, Yamada T, Takayama K, Kuriyama S, Takahata O, Karibe H, Okada Y, Xiao CY, Ma H, Narumiya S, Ushikubi F

    CIRCULATION   112 ( 1 )   84 - 92   2005.7

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    DOI: 10.1161/CIRCULATIONAHA.104.527077

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  • Thromboxane A2 and prostaglandin F2α mediate inflammatory tachycardia Reviewed

    Takayama K, Yuhki K, Ono K, Fujino T, Hara A, Yamada T, Kuriyama S, Karibe H, Okada Y, Takahata O, Taniguchi T, Iijima T, Iwasaki H, Narumiya S, Ushikubi F.

    NATURE MEDICINE   11 ( 5 )   562 - 566   2005.5

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    DOI: 10.1038/nm1231

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  • 【分子高血圧 最新の進歩】レニン分泌に関わるプロスタノイドの役割

    藤野 貴行, 長谷部 直幸, 結城 幸一, 原 明義, 中川 直樹, 福澤 純, 菊池 健次郎, 成宮 周, 牛首 文隆

    血圧   12 ( 3 )   338 - 342   2005.3

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    プロスタノイドは,プロスタグランジン(PG)とトロンボキサン(TX)よりなる,一群の生理活性物質である.一方,レニンは腎血管性高血圧症の病態形成および塩類欠乏状態における体液保持機構として中心的な役割を果たしている.また,外来性に投与されたプロスタノイドのレニン分泌促進作用の報告はあるが,腎血管性高血圧症および塩類欠乏状態でのレニン分泌調節におけるプロスタノイドの役割は不明である.そこで,本研究は,各プロスタノイド受容体を欠損するマウスを用い,プロスタノイドのレニン分泌を介した腎血管性高血圧症の病態形成における役割の解明を目指した.その結果,PGI2は,腎血管性高血圧症および塩類欠乏状態の病態形成に重要な役割を果たすことが明らかとなった.また,その作用機構として,PGI2がレニンmRNAの発現を上昇させ,レニン分泌を促進することが解明された(著者抄録)

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  • Prostaglandin receptors EP2, EP3, and IP mediate exudate formation in carrageenin-induced mouse pleurisy Reviewed

    Yuhki K, Ueno A, Naraba H, Kojima F, Ushikubi F, Narumiya S, Oh-ishi S

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   311 ( 3 )   1218 - 1224   2004.12

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    DOI: 10.1124/jpet.104.071548

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  • Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP Reviewed

    Fujino T, Nakagawa N, Yuhki K, Hara A, Yamada T, Takayama K, Kuriyama S, Hosoki Y, Takahata O, Taniguchi T, Fukuzawa J, Hasebe N, Kikuchi K, Narumiya S, Ushikubi F.

    JOURNAL OF CLINICAL INVESTIGATION   114 ( 6 )   805 - 812   2004.9

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    DOI: 10.1172/JCI200421382

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  • Prostaglandin E2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP4 Reviewed

    Xiao CY, Yuhki K, Hara A, Fujino T, Kuriyama S, Yamada T, Takayama K, Takahata O, Karibe H, Taniguchi T, Narumiya S, Ushikubi F

    CIRCULATION   109 ( 20 )   2462 - 2468   2004.5

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    DOI: 10.1161/01.CIR.0000128046.54681.97

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  • Thromboxane A2 regulates vascular tone via its inhibitory effect on the expression of inducible nitric oxide synthase Reviewed

    Yamada T, Fujino T, Yuhki K, Hara A, Karibe H, Takahata O, Okada Y, Xiao CY, Takayama K, Kuriyama S, Taniguchi T, Shiokoshi T, Ohsaki Y, Kikuchi K, Narumiya S, Ushikubi F.

    CIRCULATION   108 ( 19 )   2381 - 2386   2003.11

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    DOI: 10.1161/01.CIR.0000093194.21109.EC

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  • 【受容体・チャネル遺伝子の改変修飾と疾病・治療モデル】心血管系におけるプロスタノイドの病態生理的役割 受容体欠損マウスを用いた解析

    原 明義, 結城 幸一, 藤野 貴行, 成宮 周, 牛首 文隆

    日本薬理学雑誌   122 ( 5 )   384 - 390   2003.11

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  • Enhancement of glycolysis in cardiomyocytes elevates endothelin-1 expression through the transcriptional factor hypoxia-inducible factor-1 alpha. Reviewed

    Kakinuma Y, Miyauchi T, Suzuki T, Yuki K, Murakoshi N, Goto K, Yamaguchi I

    Clinical science (London, England : 1979)   103 Suppl 48   210S - 214S   2002.8

  • Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells Reviewed

    Fujino T, Yuhki K, Yamada T, Hara A, Takahata O, Okada Y, Xiao CY, Ma H, Karibe H, Iwashima Y, Fukuzawa J, Hasebe N, Kikuchi K, Narumiya S, Ushikubi F.

    BRITISH JOURNAL OF PHARMACOLOGY   136 ( 4 )   530 - 539   2002.6

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    DOI: 10.1038/sj.bjp.0704749

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  • Endothelin-1 production is enhanced by rotenone, a mitochondrial complex I inhibitor, in cultured rat cardiomyocytes Reviewed

    Yuhki K, Miyauchi T, Kakinuma Y, Murakoshi N, Maeda S, Goto K, Yamaguchi I, Suzuki T.

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY   38 ( 6 )   850 - 858   2001.12

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    DOI: 10.1097/00005344-200112000-00006

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  • Endothelin-1 stimulates cardiomyocyte injury during mitochondrial dysfunction in culture Reviewed

    Yuki K, Suzuki T, Katoh S, Kakinuma Y, Miyauchi T, Mitsui Y.

    EUROPEAN JOURNAL OF PHARMACOLOGY   431 ( 2 )   163 - 170   2001.11

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    DOI: 10.1016/S0014-2999(01)01434-0

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  • Roles of prostaglandin I2 and thromboxane A2 in cardiac ischemia-reperfusion injury - A study using mice lacking their respective receptors Reviewed

    Xiao CY, Hara A, Yuhki K, Fujino T, Ma H, Okada Y, Takahata O, Yamada T, Murata T, Narumiya S, Ushikubi F

    CIRCULATION   104 ( 18 )   2210 - 2215   2001.10

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  • Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation Reviewed

    Kumagai Y, Hayashi T, Miyauchi T, Endo A, Iguchi A, Kiriya-Sakai M, Sakai S, Yuki K, Kikushima M, Shimojo N.

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   281 ( 1 )   R25 - R30   2001.7

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  • Novel molecular mechanism of increased myocardial endothelin-1 expression in the failing heart involving the transcriptional factor hypoxia-inducible factor-1 alpha induced for impaired myocardial energy metabolism Reviewed

    Kakinuma Y, Miyauchi T, Yuki K, Murakoshi N, Goto K, Yamaguchi I.

    CIRCULATION   103 ( 19 )   2387 - 2394   2001.5

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  • Regulation of TNF alpha and interleukin-10 production by prostaglandins I-2 and E-2: studies with prostaglandin receptor-deficient mice and prostaglandin E-receptor subtype-selective synthetic agonists Reviewed

    S Shinomiya, H Naraba, A Ueno, Utsunomiya, I, T Maruyama, S Ohuchida, F Ushikubi, K Yuki, S Narumiya, Y Sugimoto, A Ichikawa, S Oh-ishi

    BIOCHEMICAL PHARMACOLOGY   61 ( 9 )   1153 - 1160   2001.5

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    DOI: 10.1016/S0006-2952(01)00586-X

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  • Impairment of cardiac energy metabolism in vivo causes hemodynamic abnormality and increases cardiac expression of preproendothelin-1 mRNA. Reviewed

    Murakoshi N, Miyauchi T, Kakinuma Y, Yuki K, Goto K, Yamaguchi I

    J Cardiovasc Pharmacol.   36 ( 5 )   S128 - S131   2000.11

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    DOI: 10.1097/00005344-200036051-00041

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  • Mitochondrial dysfunction of cardiomyocytes causing impairment of cellular energy metabolism induces apoptosis, and concomitant increase in cardiac endothelin-1 expression. Reviewed

    Kakinuma Y, Miyauchi T, Yuki K, Murakoshi N, Goto K, Yamaguchi I

    J Cardiovasc Pharmacol.   36 ( 5 )   S201 - S204   2000.11

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    DOI: 10.1097/00005344-200036051-00061

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  • Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts Reviewed

    Iemitsu M, Miyauchi T, Maeda S, Yuki K, Kobayashi T, Kumagai Y, Shimojo N, Yamaguchi I, Matsuda M.

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   279 ( 3 )   R951 - R959   2000.9

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  • Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in Inner Mongolia Reviewed

    Pi J, Kumagai Y, Sun G, Yamauchi H, Yoshida T, Iso H, Endo A, Yu L, Yuki K, Miyauchi T, Shimojo N.

    FREE RADICAL BIOLOGY AND MEDICINE   28 ( 7 )   1137 - 1142   2000.4

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    DOI: 10.1016/S0891-5849(00)00209-4

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  • Mitochondrial dysfunction increases expression of endothelin-1 and induces apoptosis through caspase-3 activation in rat cardiomyocytes in vitro Reviewed

    Yuki K, Miyauchi T, Kakinuma Y, Murakoshi N, Suzuki T, Hayashi J, Goto K, Yamaguchi I.

    Journal of Cardiovascular Pharmacology   36 ( 5 )   S205 - S208   2000

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    DOI: 10.1097/00005344-200036001-00101

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  • Effect of a soluble pseudo-receptor on verotoxin 2-induced toxicity Reviewed

    Mitsuko Takenaga, Rie Igarashi, Megumu Higaki, Toshiaki Nakayama, Koichi Yuki, Yutaka Mizushima

    Journal of Infection and Chemotherapy   6 ( 1 )   21 - 25   2000

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    DOI: 10.1007/s101560050044

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  • Myocardial expression of endothelin-2 is altered reciprocally to that of endothelin-1 during ischemia of cardiomyocytes in vitro and during heart failure in vivo Reviewed

    Kakinuma Y, Miyauchi T, Kobayashi T, Yuki K, Maeda S, Sakai S, Goto K, Yamaguchi I.

    LIFE SCIENCES   65 ( 16 )   1671 - 1683   1999.9

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    DOI: 10.1016/S0024-3205(99)00416-6

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  • Phosphorylation of a170 stress protein by casein kinase II-like activity in macrophages Reviewed

    Toru Yanagawa, Koichi Yuki, Hiroshi Yoshida, Shiro Bannai, Tetsuro Ishii

    Biochemical and Biophysical Research Communications   241 ( 1 )   157 - 163   1997.12

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    DOI: 10.1006/bbrc.1997.7783

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  • Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages(共著). Reviewed

    Ishii T, Yanagawa T, Yuki K, Kawane T, Yoshida H, Bannai S.

    Biochemical and Biophysical Research Communications   232 ( 1 )   33 - 37   1997

  • Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56(lck)-associated protein in response to oxidative stress Reviewed

    T Ishii, T Yanagawa, T Kawane, K Yuki, J Seita, H Yoshida, S Bannai

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   226 ( 2 )   456 - 460   1996.9

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    DOI: 10.1006/bbrc.1996.1377

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MISC

  • 卵巣におけるプロスタグランジンD2合成遺伝子の発現解析

    今道 力敬, 結城 幸一, 矢澤 隆志, 牛首 文隆

    日本内分泌学会雑誌   96 ( 1 )   340 - 340   2020.8

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  • Prostaglandin F-2 alpha potentiates platelet aggregation via prostaglandin E-2 and thromboxane A(2) receptors

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Yoshitaka Imamichi, Fumiaki Kojima, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   133 ( 3 )   S109 - S109   2017.3

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  • Promoting effect of prostaglandin F-2 alpha on platelet aggregation

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Yoshitaka Imamichi, Fumiaki Kojima, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 3 )   S172 - S172   2016.3

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  • 心脈管作動物質プロスタノイドの生体における役割 循環器疾患の病態形成におけるプロスタノイドの役割

    結城 幸一, 柏木 仁, 今道 力敬, 中川 直樹, 藤野 貴行, 川辺 淳一, 牛首 文隆

    血管   39 ( 1 )   26 - 26   2016.1

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  • Cigarette smoke extract inhibits platelet aggregation

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 )   S144 - S144   2015.7

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  • Protective Effects of the Postaglandin I-2-I-p Signal in Nonalcoholic Steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Hitoshi Kashiwagi, Toshikatsu Okumura, Fumitaka Ushikubi

    GASTROENTEROLOGY   148 ( 4 )   S968 - S968   2015.4

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  • Protective Effect of the Postaglandin I2-IP Signal Through the Suppression of Cyotokines Expression in Nonalcoholic Steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Fumitaka Ushikubi

    GASTROENTEROLOGY   146 ( 5 )   S958 - S958   2014.5

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  • Thromboxane A(2) plays a critical role in reduction of the anti-platelet effect of prostaglandin I-2 receptor agonist beraprost after repeated administration

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Yoshiki Sakai, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124   136P - 136P   2014

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  • Roles of the prostaglandin I-2-IP system in nonalcoholic steatohepatitis

    Shima Kumei, Yuhki Koh-ichi, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124   84P - 84P   2014

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  • Protective Effect of the Postaglandin I2-IP Signal in Mcd Diet-Induced Nonalcoholic Steatohepatitis in Mice

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Fumitaka Ushikubi

    GASTROENTEROLOGY   144 ( 5 )   S76 - S77   2013.5

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  • 非アルコール性脂肪性肝炎の発症・進展におけるプロスタグランジンI2の役割解明

    粂井 志麻, 結城 幸一, 小島 史章, 柏木 仁, 奥村 利勝, 牛首 文隆

    日本薬理学雑誌   141 ( 1 )   8P - 8P   2013.1

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  • Role of the prostaglandin E-2 receptor subtype EP1 in cisplatin-induced nephrotoxicity

    Fumiaki Kojima, Koh-ichi Yuhki, Hitoshi Kashiwagi, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   167P - 167P   2013

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  • Roles of the prostaglandin I-2-IP system in the development of nonalcoholic steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   70P - 70P   2013

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  • プロスタグランジンE2(PGE2)のその受容体サブタイプEP4アゴニストの腎間質線維化抑制効果 in vitroでの検討

    鹿原 真樹, 中川 直樹, 松木 孝樹, 珍田 純子, 藤野 貴行, 結城 幸一, 牛首 文隆, 長谷部 直幸

    日本腎臓学会誌   54 ( 3 )   239 - 239   2012.4

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  • 腎間質線維化におけるプロスタグランジンE2-EP4系の役割

    中川 直樹, 結城 幸一, 小島 史章, 柏木 仁, 藤野 貴行, 川辺 淳一, 長谷部 直幸, 牛首 文隆

    日本薬理学雑誌   139 ( 1 )   8P - 8P   2012.1

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  • トロンボキサンA2合成酵素の阻害はプロスタグランジンI2受容体の脱感作を抑制する

    柏木 仁, 結城 幸一, 小島 史章, 酒井 芳紀, 牛首 文隆

    日本薬理学雑誌   139 ( 1 )   7P - 7P   2012.1

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  • Role of prostaglandin l(2) in nonalcoholic steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shu Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   79P - 79P   2012

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  • Inhibition of thromboxane A(2) synthase prevents reduction in the anti-platelet effect of a prostaglandin l(2) receptor agonist after repeated administration

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Yoshiki Sakai, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   75P - 75P   2012

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  • 非アルコール性脂肪性肝炎の発症・進展におけるプロスタグランジンI2の役割解明

    粂井 志麻, 結城 幸一, 柏木 仁, 小島 史章, 奥村 利勝, 牛首 文隆

    日本薬理学雑誌   137 ( 1 )   11P - 11P   2011.1

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  • Role of prostaglandin I-2 in nonalcoholic steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   115   67P - 67P   2011

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  • プロスタグランジンE2受容体サブタイプEP4の脳梗塞病態形成における役割

    小島 史章, 結城 幸一, 李 暁正, 鈴木 康博, 柏木 仁, 牛首 文隆

    日本薬理学雑誌   135 ( 1 )   2P - 2P   2010.1

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  • Role of the prostaglandin E-2 receptor subtype EP4 in ischemic brain injury

    Fumiaki Kojima, Akimasa Ri, Koh-ichi Yuhki, Yasuhiro Suzuki, Hitoshi Kashiwagi, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   79P - 79P   2010

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  • The Cardioprotective Effect of Prostaglandin E-2/EP4 System is Important for the Late Phase Preconditioning

    Takayasu Kanno, Jun-ichi Kawabe, Koh-ichi Yuhki, Naofumi Takehara, Fumitaka Ushikubi, Naoyuki Hasebe

    CIRCULATION   120 ( 18 )   S784 - S784   2009.11

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  • Selective activation of the prostaglandin E-2 receptor subtype EP2 or EP4 leads to an inhibition of platelet aggregation

    Hitoshi Kashiwagi, Shuhko Kuriyama, Koh-ichi Yuhki, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   62P - 62P   2009

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  • Nitric oxide (NO) plays a role in inflammatory tachycardia

    Asako Kanai, Koh-ichi Yuhki, Jun-ichi Kawabe, Yasuhiro Suzuki, Hitoshi Kashiwagi, Kazuo Sengoku, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   69P - 69P   2009

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  • Roles of the prostanoids in the cardiovascular diseases

    Koh-Ichi Yuhki, Fumitaka Ushikubi

    Seikagaku   81 ( 2 )   84 - 94   2009

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  • Role of endogenous prostaglandin I-2 in the progression of vascular remodeling

    Osamu Takahata, Koh-ichi Yuhki, Jun-ichi Kawabe, Yasuhiro Suzuki, Hiroshi Iwasaki, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   113P - 113P   2008

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  • Deletion of prostacyclin-receptor in bone marrow attenuates differentiation of endothelial progenitor cells, and enhances vascular intimal hyperplasia

    Jun-ichi Kawabe, Koh-ichi Yuhki, Takayasu Kannno, Naoyuki Hasebe, Fumitaka Ushikubi

    CIRCULATION   116 ( 16 )   268 - 268   2007.10

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  • プロスタノイドの糖尿病性および腎摘出後腎症における役割 受容体欠損マウスを用いた検討

    藤野 貴行, 阿部 和利, 中川 直樹, 長谷部 直幸, 結城 幸一, 川辺 淳一, 菊池 健次郎, 牛首 文隆

    日本腎臓学会誌   49 ( 3 )   337 - 337   2007.4

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  • プロスタグランジンE2はその受容体サブタイプEP3を介して虚血-再灌流傷害から心臓を保護する(Prostaglandin E2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP3)

    Yuhki Koh-ichi, Xiao Chun Yang, Hara Akiyoshi, Kawabe Jun-ichi, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   103 ( Suppl.I )   113 - 113   2007.2

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  • Ionic mechanisms underlying the positive chronotropic action of PGF(2 alpha a) and TXA PGF(2) in isolated guinea-pig sinoatrial node cells.

    Kyoichi Ono, Susumu Fujisawa, Koh-Ichi Yuhki, Fumitaka Ushikubi, Toshihiko Iijima

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   93P - 93P   2007

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  • Decreased susceptibility to glomerular hypertrophy and albuminuria in thromboxane A(2) receptor deficient mice

    Takayuki Fujino, Kazutoshi Abe, Naoki Nakagawa, Kohichi Yuhki, Junichi Kawabe, Jun Fukuzawa, Naoyuki Hasebe, Kenjiro Kikuchi, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF HYPERTENSION   24   293 - 293   2006.12

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  • Role of prostanoids in inflammatory tachycardia: A reply to the letter of Dr. Eugene Nalivaiko

    K Yuhki, J Kawabe, F Ushikubi

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   290 ( 6 )   R1751 - R1751   2006.6

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    DOI: 10.1152/ajpregu.00019.2006

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  • 血管病の分子メカニズムと新しい治療戦略 心血管系におけるプロスタノイドの役割(Molecular mechanism and novel therapeutic strategies of vascular diseases: Roles of the prostanoids in the cardiovascular system)

    Yuhki Koh-ichi, Kawabe Jun-ichi, Takahata Osamu, Hara Akiyoshi, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   100 ( Suppl.I )   43P - 43P   2006.2

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  • プロスタグランジンE2はマウス脳血栓症モデルにおいてEP4を介して虚血障害を悪化させる(Prostaglandin E2 aggravates ischemic injury via EP4 in a murine model of cerebral thrombosis)

    Ri Akimasa, Yuhki Koh-ichi, Kawabe Jun-ichi, Hara Akiyoshi, Hosoki Yayoi, Takahata Osamu, Iwasaki Hiroshi, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   100 ( Suppl.I )   261P - 261P   2006.2

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  • 脳血栓症の病態形成におけるPGE2-EP4系の役割

    李 暁正, 結城 幸一, 原 明義, 岩崎 寛, 成宮 周, 牛首 文隆

    日本薬理学雑誌   127 ( 1 )   9P - 9P   2006.1

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  • The prostaglandin E-2-EP4 system protects the heart from ischemia-reperfusion injury Reviewed

    K. Yuhki, C-Y. Xiao, A. Hara, T. Fujino, S. Narumiya, F. Ushikubi

    ADVANCES IN HEART DISEASE   337 - +   2006

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  • Key roles of complement activation and prostaglandin I-2 for exudate formation in zymosan-induced mouse pleurisy

    K Yuhki, H Naraba, S Narumiya, S Oh-Ishi, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   239P - 239P   2006

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  • Thromboxane A(2) inhibits expression of inducible nitric oxide synthase and regulates vascular tone Reviewed

    T. Yamada, T. Fujino, K. Yuhki, A. Hara, K. Matsubara, S. Narumiya, F. Ushikubi

    ADVANCES IN HEART DISEASE   75 - 78   2006

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  • Roles of the prostanoids in the cardiovascular system

    K Yuhki, J Kawabe, O Takahata, A Hara, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   43P - 43P   2006

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  • 【プロスタグランジンの多様性】循環器系におけるプロスタノイドの役割

    結城 幸一, 藤野 貴行, 川辺 淳一, 原 明義, 牛首 文隆

    炎症と免疫   14 ( 1 )   59 - 65   2005.12

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  • Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I-2 receptor IP

    T Fujino, N Hasebe, J Fukuzawa, K Kikuchi, K Yuhki, F Ushikubi, S Narumiya

    CIRCULATION   112 ( 17 )   U317 - U317   2005.10

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  • 【リピッドメディエーターとVascular Biology】心血管系におけるプロスタグランジンの役割 受容体欠損マウスから Reviewed

    原 明義, 藤野 貴行, 牛首 文隆, 結城 幸一, 成宮 周

    血管医学   6 ( 4 )   337 - 349   2005.8

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  • 腎繊維化に関わるプロスタノイドの役割

    阿部 和利, 藤野 貴行, 中川 直樹, 結城 幸一, 原 明義, 長谷部 直幸, 菊池 健次郎, 牛首 文隆

    日本腎臓学会誌   47 ( 3 )   295 - 295   2005.5

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  • 全身性炎症疾患の病態生理 誘導型NOSの発現抑制を介したTXA2の血管緊張調節

    山田 武宏, 結城 幸一, 原 明義, 松原 和夫, 牛首 文隆

    日本薬学会年会要旨集   125年会 ( 2 )   102 - 102   2005.3

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  • 肝再生におけるプロスタグランジンI2-IP系の役割(Role of the prostaglandin I2-1P system in liver regeneration)

    Hosoki Yayoi, Yuhki Koh-ichi, Hara Akiyoshi, Ri Akimasa, Kohgo Yutaka, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   97 ( Suppl.I )   125P - 125P   2005.3

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  • 【分子高血圧 最新の進歩】レニン分泌に関わるプロスタノイドの役割

    藤野 貴行, 長谷部 直幸, 結城 幸一, 原 明義, 中川 直樹, 福澤 純, 菊池 健次郎, 成宮 周, 牛首 文隆

    血圧   12 ( 3 )   338 - 342   2005.3

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  • マウス肝再生におけるプロスタグランジンI2-IP系の役割

    細木 弥生, 結城 幸一, 原 明義, 大蔵 暁正, 高後 裕, 成宮 周, 牛首 文隆

    日本薬理学雑誌   125 ( 1 )   10P - 10P   2005.1

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  • Roles of prostanoids in pressure overload-induced cardiomyocyte hypertrophy and cardiac fibrosis in mice

    A Hara, K Yuhki, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   193P - 193P   2005

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  • Roles of the prostanoids in the cardiovascular diseases

    K Yuhki, A Hara, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   42P - 42P   2005

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  • Prostaglandin receptors EP2, EP3, and IP mediate exudate formation in carrageenin-induced mouse pleurisy

    K Yuhki, A Ueno, H Naraba, F Kojima, F Ushikubi, S Narumiya, S Oh-ishi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   251P - 251P   2005

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  • Effects of prostaglandin D-2 on blood pressure and heart rate

    H Karibe, K Yuhki, A Hara, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   179P - 179P   2005

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  • 腎切除後の腎肥大におけるトロンボキサンA2及びプロスタグランジンI2の役割 プロスタノイド受容体欠失マウスを用いた研究(Role of thromboxane A2 and prostaglandin I2 in renal hypertrophy after renal ablation: study using prostanoids receptors deficient mice)

    Fujino Takayuki, Yuhki Koh-ichi, Hara Akiyoshi, Nakagawa Naoki, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Ushikubi Fumitaka

    日本高血圧学会総会プログラム・抄録集   27回   239 - 239   2004.10

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  • プロスタグランジンE2はその受容体サブタイプEP4を介して腎間質線維化を抑制する

    中川 直樹, 藤野 貴行, 結城 幸一, 原 明義, 牛首 文隆, 成宮 周, 長谷部 直幸, 菊池 健次郎

    日本腎臓学会誌   46 ( 3 )   198 - 198   2004.4

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  • 腎切除後の腎肥大におけるトロンボキサンA2及びプロスタグランジンI2の役割(Roles of thromboxane A2 and prostaglandin 12 in renal hypertrophy after renal ablation)

    Fujino Takayuki, Nakagawa Naoki, Yuhki Koh-ichi, Hara Akiyoshi, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Ushikubi Fumitaka

    日本腎臓学会誌   46 ( 3 )   174 - 174   2004.4

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  • prostaglandin E2受容体サブタイプEP4に対するアゴニストは四塩化炭素誘導急性障害から肝臓を保護する(An agonist for the prostaglandin E2 receptor subtype EP4 protects the liver from carbon tetrachloride-induced acute injury)

    Okada Yuji, Yuhki Koh-ichi, Nakanishi Katsura, Hosoki Yayoi, Hara Akiyoshi, Fujino Takayuki, Kohgo Yutaka, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   94 ( Suppl.I )   253P - 253P   2004.3

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  • 腎部分切除後の糸球体再生におけるトロンボキサンA2及びプロスタグランジンI2により調節される血小板活性の役割(Role of Platelet Activity Regulated by Thromboxane A2 and Prostaglandin I2 in Glomerular Regeneration after Renal Ablation)

    Fujino Takayuki, Nakagawa Naoki, Yuhki Kohichi, Hara Akiyoshi, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Ushikubi Fumitaka

    Circulation Journal   68 ( Suppl.I )   412 - 412   2004.3

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  • prostaglandin I2受容体を欠くマウスにおける圧力過重負荷に応答しての心臓肥大の増加(Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin l2 receptor)

    Hara Akiyoshi, Yuhki Koh-ichi, Fujino Takayuki, Yamada Takehiro, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   94 ( Suppl.I )   267P - 267P   2004.3

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  • 腎血管性高血圧におけるレニン上昇および高血圧とループ利尿薬併用低Na食に対するプロスタサイクリンの役割(Roles of Prostacyclin in Renin Elevation and Hypertension in Reno-vascular Hypertension and on Low Sodium Diet with Loop Diuretics)

    Fujino Takayuki, Nakagawa Naoki, Yuhki Koh-ichi, Hara Akiyoshi, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Ushikubi Fumitaka

    Circulation Journal   68 ( Suppl.I )   630 - 631   2004.3

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  • prostanoidsによるシクロオキシゲナーゼ2発現の調節(Regulation of cyclooxygenase-2 expression by prostanoids)

    Yamada Takehiro, Fujino Takayuki, Yuhki Koh-ichi, Hara Akiyoshi, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   94 ( Suppl.I )   213P - 213P   2004.3

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  • プロスタグランジンE2はEP4受容体を介してケモカイン産生と腎線維化を抑制する EP4欠損マウスによる研究(Prostaglandin E2 Suppresses Chemokines Production and Renal Fibrosis through the EP4 Receptor: Studies Using EP4 Deficient Mice)

    Nakagawa Naoki, Fujino Takayuki, Yuki Koichi, Hara Akiyoshi, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Narumiya Shuh, Ushikubi Fumitaka

    Circulation Journal   68 ( Suppl.I )   360 - 360   2004.3

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  • prostaglandin E2はその受容体サブタイプEP4を介して腎臓線維症を抑制する(Prostaglandin E2 Suppresses Renal Fibrosis via its Receptor Subtype EP4)

    Nakagawa Naoki, Fujino Takayuki, Yuhki Koh-ichi, Hara Akiyoshi, Hasebe Naoyuki, Kikuchi Kenjiro, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   94 ( Suppl.I )   259P - 259P   2004.3

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  • 血管リモデリング発生早期における内因性プロスタグランジンI2の役割

    高畑 治, 岩崎 寛, 藤野 貴行, 結城 幸一, 原 明義, 高山 浩二, 牛首 文隆

    麻酔   53 ( 2 )   218 - 218   2004.2

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  • 血小板凝集反応におけるプロスタグランジン(PG)E2の作用

    栗山 周子, 結城 幸一, 山田 武宏, 藤野 貴行, 原 明義, 成宮 周, 牛首 文隆

    日本薬理学雑誌   123 ( 1 )   5P - 5P   2004.1

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    DOI: 10.1254/fpj.123.5

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  • 腎線維化におけるプロスタグランジンE2の役割

    中川 直樹, 藤野 貴行, 結城 幸一, 原 明義, 長谷部 直幸, 菊池 健次郎, 成宮 周, 牛首 文隆

    日本薬理学雑誌   123 ( 1 )   19P - 19P   2004.1

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  • 虚血-再灌流障害におけるPGE2のEP4を介した心筋保護作用 Reviewed

    結城 幸一, 肖 春陽, 原 明義, 藤野 貴行, 成宮 周, 牛首 文隆

    日本薬理学雑誌   123 ( 1 )   2P - 2P   2004.1

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  • プロスタノイドによるCyclooxygenase-2の発現調節

    山田 武宏, 藤野 貴行, 結城 幸一, 原 明義, 成宮 周, 牛首 文隆

    日本薬理学雑誌   123 ( 1 )   5P - 5P   2004.1

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    DOI: 10.1254/fpj.123.5

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  • マウスの心筋細胞肥大及び非心筋細胞増殖に及ぼすプロスタグランジンI2の作用

    原 明義, 結城 幸一, 藤野 貴行, 山田 武宏, 成宮 周, 牛首 文隆

    日本薬理学雑誌   123 ( 1 )   3P - 3P   2004.1

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  • Effects of the prostanoids on blood pressure and heart rate: an analysis using mice lacking the prostanoid receptors

    H Karibe, A Hara, K Yuhki, T Fujino, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   94   266P - 266P   2004

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  • 腎血管性高血圧のレニン上昇及び高血圧におけるプロスタサイクリンの役割及びループ利尿剤併用低ナトリウム食について(Roles of prostacyclin in renin elevation and hypertension in renovascular hypertension and on low sodium diet with loop diuretics)

    Fujino Takayuki, Nakagawa Naoki, Yuhki Koh-Ichi, Hara Akiyoshi, Fukuzawa Jun, Hasebe Naoyuki, Kikuchi Kenjiro, Ushikubi Fumitaka

    日本高血圧学会総会プログラム・抄録集   26回   221 - 221   2003.10

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  • 糸球体硬化におけるプロスタノイドの役割

    藤野 貴行, 中川 直樹, 結城 幸一, 原 明義, 福沢 純, 長谷部 直幸, 菊池 健次郎, 牛首 文隆

    日本内分泌学会雑誌   79 ( 2 )   529 - 529   2003.9

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  • トロンボキサンA2による誘導型一酸化窒素合成酵素の発現抑制を介した血管張力の調節(Thromboxane A2 regulates vascular tone via the inhibitory effect on the expression of inducible nitric oxide synthase)

    Yamada Takehiro, Fujino Takayuki, Yuhki Koh-ichi, Hara Akiyoshi, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   91 ( Suppl.I )   76P - 76P   2003.3

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  • プロスタグランジンF2αとトロンボキサンA2のマウス心拍調節における役割

    高山 浩二, 結城 幸一, 原 明義, 藤野 貴行, 山田 武宏, 牛首 文隆, 高畑 治, 岩崎 寛, 成宮 周

    麻酔   52 ( 3 )   324 - 324   2003.3

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  • 胸部大動脈の収縮・弛緩を仲介するプロスタノイド受容体について(Receptors mediating prostanoid-induced contraction or relaxation of the thoracic aorta)

    Karibe Hideji, Hara Akiyoshi, Yuhki Koh-ichi, Fujino Takayuki, Narumiya Shuh, Ushikubi Fumitaka

    Journal of Pharmacological Sciences   91 ( Suppl.I )   234P - 234P   2003.3

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  • 圧負荷による心筋細胞肥大及び心線維化における内因性プロスタグランジンI2の役割 Reviewed

    原 明義, 結城 幸一, 藤野 貴行, 高畑 治, 成宮 周, 牛首 文隆

    日本薬理学雑誌   121 ( 1 )   15P - 15P   2003.1

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  • プロスタグランジンF2αとトロンボキサンA2のマウス心拍調節における役割

    高山 浩二, 結城 幸一, 原 明義, 藤野 貴行, 山田 武宏, 高畑 治, 岩崎 寛, 成宮 周, 牛首 文隆

    日本薬理学雑誌   121 ( 1 )   15P - 15P   2003.1

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  • PGE2-EP4系の虚血-再灌流障害における心筋保護作用 Reviewed

    結城 幸一, 肖 春陽, 原 明義, 栗山 周子, 藤野 貴行, 成宮 周, 牛首 文隆

    日本薬理学雑誌   121 ( 1 )   15P - 15P   2003.1

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  • Thromboxane A(2) regulates vascular tone via the inhibitory effect on the expression of inducible nitric oxide synthase.

    T Yamada, T Fujino, K Yuhki, A Hara, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   91   76P - 76P   2003

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    DOI: 10.1161/01.CIR.0000093194.21109.EC

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  • Pathophysiological roles of prostanoids in cardiovascular system: Studies using mice deficient in prostanoid receptors.

    A Hara, K Yuhki, T Fujino, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   91   40P - 40P   2003

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  • Roles of prostanoids in renovascular hypertension.

    T Fujino, K Yuhki, A Hara, N Hasebe, K Kikuchi, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   91   257P - 257P   2003

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  • Thromboxane A(2) regulates vascular tone via the inhibitory effect on the expression of inducible nitric oxide synthase.

    T Yamada, T Fujino, K Yuhki, A Hara, S Narumiya, F Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   91   76P - 76P   2003

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    DOI: 10.1161/01.CIR.0000093194.21109.EC

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  • 腎血管性高血圧症におけるプロスタノイドの役割

    藤野 貴行, 結城 幸一, 原 明義, 長谷部 直幸, 菊池 健次郎, 牛首 文隆

    日本高血圧学会総会プログラム・抄録集   25回   83 - 83   2002.10

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  • Prostanoid EP3ならびにEP4受容体の刺激はマウスの心筋の虚血再灌流障害を減弱する(Stimulation of prostanoid EP3 and EP4 receptors attenuates myocardial ischemia/reperfusion injury in mice)

    Xiao Chun-Yang, Hara Akiyoshi, Yuhki Koh-ichi, Fujino Takayuki, Narumiya Shuh, Ushikubi Fumitaka

    The Japanese Journal of Pharmacology   88 ( Suppl.I )   263P - 263P   2002.3

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  • 腎血管性高血圧におけるProstanoidの役割(Roles of the prostanoids in renovascular hypertension)

    Fujino Takayuki, Yamada Takehiro, Okada Yuji, Takayama Kouji, Yuhki Koh-ichi, Hara Akiyoshi, Takahata Osamu, Kikuchi Kenjiro, Narumiya Shuh, Ushikubi Fumitaka

    The Japanese Journal of Pharmacology   88 ( Suppl.I )   206P - 206P   2002.3

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  • 血管平滑筋細胞の肥大・増殖におけるプロスタノイドの役割

    藤野 貴行, 山田 武宏, 結城 幸一, 原 明義, 菊池 健次郎, 成宮 周, 牛首 文隆

    血管   25 ( 1 )   34 - 34   2002.1

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  • Prostaglandin receptors IP and EP mediating regulation of tumor necrosis factor-alpha and interleukin-10 production Reviewed

    H Naraba, S Shinomiya, A Ueno, Utsunomiya, I, F Ushikubi, K Yuki, S Narumiya, Y Sugimoto, A Ichikawa, T Maruyama, S Ohuchida, S Oh-Ishi

    OXYGEN AND LIFE: OXYGENASES, OXIDASE AND LIPID MEDIATORS   1233   479 - 484   2002

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  • Cardiac hypertrophic response by acute pressure-overload is reduced in cardiomyocyte-specific endothelin-1 knockout mice in which coronary endothelial endothelin-1 is not knockedout

    N Murakoshi, T Miyauchi, Y Kisanuki, Y Kakinuma, K Yuki, Yamaguchi, I, K Goto, M Yanagisawa

    CIRCULATION   104 ( 17 )   86 - 86   2001.10

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  • プロスタノイドEP3及びEP4受容体欠損マウスにおける心筋虚血/再灌流障害に対する感受性の増加(Increased susceptibility to myocardial ischemia/reperfusion injury in mice lacking the prostanoid EP3 and EP4 receptors)

    Xiao Chun-yang, Hara Akiyoshi, Yuhki Koh-ichi, Fujino Takayuki, Ushikubi Fumitaka

    The Japanese Journal of Pharmacology   85 ( Suppl.I )   82P - 82P   2001.3

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  • 両受容体欠失マウスを用いた虚血/再灌流障害心筋におけるプロスタグランジンI2ならびにトロンボキサンA2の役割の解析(Analysis of roles of prostaglandin I2 and thromboxane A2 in cardiac ischemia/reperfusion injury using mice lacking each of their respective receptors)

    Xiao Chun-yang, Yuhki Koh-ichi, Hara Akiyoshi, Fujino Takayuki, Ushikubi Fumitaka

    The Japanese Journal of Pharmacology   85 ( Suppl.I )   80P - 80P   2001.3

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  • 心筋の虚血-再灌流障害におけるプロスタグランジンI2とトロンボキサンA2の役割

    肖 春陽, 原 明義, 結城 幸一, 藤野 貴行, 牛首 文隆

    日本薬理学雑誌   117 ( 2 )   12P - 12P   2001.2

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  • 圧負荷による心肥大形成におけるプロスタグランジンI2の役割

    原 明義, 結城 幸一, 藤野 貴行, 高畑 治, 牛首 文隆

    日本薬理学雑誌   117 ( 2 )   12P - 12P   2001.2

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  • 炎症急性期におけるプロスタグランジンF2αとトロンボキサンA2の陽性変時作用

    高山 浩二, 結城 幸一, 原 明義, 藤野 貴行, 山田 武宏, 高畑 治, 岩崎 寛, 成宮 周, 牛首 文隆

    日本薬理学雑誌   119 ( 1 )   4P - 4P   2001.1

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  • プロスタグランジンF2αとトロンボキサンA2の心肥大における役割 Reviewed

    結城 幸一, 原 明義, 藤野 貴行, 成宮 周, 牛首 文隆

    日本薬理学雑誌   119 ( 1 )   5P - 5P   2001.1

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  • プロスタグランジンのEP3及びEP4受容体を介した虚血心筋保護作用

    肖 春陽, 原 明義, 結城 幸一, 藤野 貴行, 成宮 周, 牛首 文隆

    日本薬理学雑誌   119 ( 1 )   5P - 5P   2001.1

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  • 誘導型一酸化窒素合成酵素の発現におけるトロンボキサンA2及びプロスタグランジンI2の役割

    山田 武宏, 藤野 貴行, 結城 幸一, 原 明義, 成宮 周, 牛首 文隆

    日本薬理学雑誌   119 ( 1 )   4P - 4P   2001.1

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  • マウス大動脈平滑筋細胞の肥大,増殖におけるプロスタノイド受容体を介した作用の役割 受容体欠損マウスを用いた検討

    藤野 貴行, 山田 武宏, 結城 幸一, 原 明義, 高畑 治, 成宮 周, 牛首 文隆

    日本薬理学雑誌   119 ( 1 )   5P - 5P   2001.1

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  • Vascular remodeling after vascular injury of the carotid artery is enhanced in endothelin-B receptor-deficient mice.

    N Murakoshi, T Miyauchi, Y Kakinuma, K Yuki, K Goto, M Yanagisawa, Yamaguchi, I

    CIRCULATION   102 ( 18 )   171 - 171   2000.10

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  • Hypoxia-inducible factor (HIF)-1 alpha, which activates glycolytic system adaptively in the impaired energy metabolism, maladaptively increases endothelin-1 mRNA expression in the failing heart.

    Y Kakinuma, T Miyauchi, K Yuki, N Murakoshi, K Goto, Yamaguchi, I

    CIRCULATION   100 ( 18 )   419 - 419   1999.11

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  • 心筋の好気的エネルギー代謝障害による新しい心不全モデルの確立 : 新モデル動物の不全心筋におけるendothelin-1(ET-1)、atrial natriuretic peptide(ANP)mRNAの著明な発現増大とアポトーシスの存在

    村越,伸行, 宮内,卓, 柿沼,由彦, 結城,幸一, 酒井,俊, 山口,巖, 杉下,靖郎

    Japanese circulation journal   63 ( 1 )   377   1999.3

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  • 【内因性生理活性物質の循環器疾患診療への応用 基礎から臨床まで】エンドセリン

    18 ( 12 )   1116 - 1119   1998.12

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  • 心臓でのendothelin(ET)-2の発現変化は、ET-1の発現変化と相反するパターンをとる。 : ET-2の不全心における発現低下と、培養心筋細胞での低酸素曝露に対する発現上昇 Reviewed

    柿沼,由彦, 後藤,勝年, 宮内,卓, 酒井,俊, 小林,勉, 下條,信威, 結城,幸一, 山口,巖, 杉下,靖郎

    Japanese circulation journal   62 ( 0 )   421   1998.2

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Presentations

  • Role of prostanoids in hepatic stellate cell function International conference

    Yuhki K., Ohkubo T., Nakayama K., Narumiya S., Ushikubi F.

    第95回日本薬理学会年会  2022.3  日本薬理学会

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    Event date: 2022.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡  

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  • Potentiating effect of prostaglandin F2alpha on platelet aggregation in mice International conference

    Kashiwagi H., Yuhki K., Imamichi Y., Kojima F., Kumei S., Narumiya S., Ushikubi F.

    18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY  International Union of Basic and Clinical Pharmacology

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    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Venue:Kyoto, Japan  

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  • Up-regulation of colonic Th1/Th17 cytokines is associated with increased severity of experimental colitis in mice lacking microsomal prostaglandin E synthase-1 International conference

    Sekiya H., Nakamura M., Maehana S., Kashiwagi H., Imamichi Y., Yuhki K., Ushikubi F., Ichikawa T., Kitasato H., Kojima F.

    18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY  International Union of Basic and Clinical Pharmacology

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    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Venue:Kyoto, Japan  

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  • Prostaglandin F2α potentiates platelet aggregation via prostaglandin E2 and thromboxane A2 receptors International conference

    柏木仁, 結城幸一, 今道力敬, 小島史章, 粂井志麻, 成宮周, 牛首文隆

    第90回日本薬理学会年会  日本薬理学会

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    Event date: 2017.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:長崎  

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  • Roles of prostanoids in organ fibrosis International conference

    結城幸一, 柏木仁, 今道力敬, 粂井志麻, 中川直樹, 成宮周, 牛首文隆

    第90回日本薬理学会年会  日本薬理学会

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    Event date: 2017.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:長崎  

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  • Roles of the prostaglandin I2 in nonalcoholic steatohepatitis International conference

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Yoshitaka Imamichi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    第90回日本薬理学会年会  日本薬理学会

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    Event date: 2017.3

    Language:English   Presentation type:Symposium, workshop panel (public)  

    Venue:長崎  

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  • タバコ煙抽出物のCOX活性阻害を介した血小板凝集抑制作用

    柏木仁, 結城幸一, 今道力敬, 小島史章, 粂井志麻, 成宮周, 牛首文隆

    第67回日本薬理学会北部会  日本薬理学会

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    Event date: 2016.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:札幌  

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  • Promoting effect of prostaglandin F2α on platelet aggregation International conference

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Yoshitaka Imamichi, Fumiaki Kojima, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    第89回日本薬理学会年会  公益社団法人日本薬理学会

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    Event date: 2016.3

    Language:English   Presentation type:Poster presentation  

    Venue:横浜市  

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  • 循環器疾患の病態形成におけるプロスタノイドの役割

    結城幸一, 柏木仁, 今道力敬, 中川直樹, 藤野貴行, 川辺淳一, 牛首文隆

    第45回日本心脈管作動物質学会  日本心脈管作動物質学会

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    Event date: 2016.2

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:徳島  

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  • タバコ煙抽出液は血小板凝集を抑制する International conference

    柏木仁, 結城幸一, 今道力敬, 小島史章, 粂井志麻, 成宮周, 牛首文隆

    第66回日本薬理学会北部会  公益社団法人日本薬理学会

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    Event date: 2015.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:富山市  

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  • ヒト生殖腺における11-ケトテストステロンの合成とその機能

    今道力敬, 矢澤隆志, 結城幸一, 柏木仁, 宮本薫, 牛首文隆

    第66回日本薬理学会北部会  公益社団法人日本薬理学会

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    Event date: 2015.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:富山市  

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  • Protective effects of the prostaglandin I2-IP signal in nonalcoholic steatohepatitis International conference

    Shima Kumei, Koh-ichi Yuhki, Hitoshi Kashiwagi, Toshikatsu Okumura, Fumitaka Ushikubi

    消化器病週間  American Gastroenterological Association

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    Event date: 2015.5

    Language:English   Presentation type:Poster presentation  

    Venue:Washington, D.C.  

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  • Roles of the prostaglandin I2-IP system in nonalcoholic steatohepatitis International conference

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    第88回日本薬理学会年会  公益社団法人日本薬理学会

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    Event date: 2015.3

    Language:English   Presentation type:Oral presentation (general)  

    Venue:名古屋  

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  • Cigarette smoke extract inhibits platelet aggregation International conference

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    第88回日本薬理学会年会  公益社団法人日本薬理学会

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋  

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  • 血小板凝集に及ぼすタバコ煙抽出液の作用

    柏木仁, 結城幸一, 小島史章, 粂井志麻, 成宮周, 牛首文隆

    第24回日本循環薬理学会 

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    Event date: 2014.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:山形  

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  • タバコ煙抽出液の血小板凝集抑制作用

    柏木仁, 結城幸一, 小島史章, 粂井志麻, 牛首文隆

    第65回日本薬理学会北部会 

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    Event date: 2014.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福島  

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  • 非アルコール性脂肪性肝炎におけるプロスタノイドの役割解明

    結城幸一, 粂井志麻, 柏木仁, 小島史章, 成宮周, 牛首文隆

    第65回日本薬理学会北部会  第65回日本薬理学会北部会

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    Event date: 2014.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福島市  

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  • Protective effect of the postaglandin I2-IP signal through the suppression of cyotokines expression in nonalcoholic steatohepatitis International conference

    Kumei S., Yuhki K., Kojima F., Kashiwagi H., Okumura T., Narumiya S., Ushikubi F.

    Digestive Disease Week 

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    Event date: 2014.5

    Language:English   Presentation type:Poster presentation  

    Venue:Chicago  

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  • Thromboxane A2 plays a critical role in reduction of the anti-platelet effect of prostaglandin I2 receptor agonist beraprost after repeated administration International conference

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Yoshiki Sakai, Shuh Narumiya, Fumitaka Ushikubi

    第87回日本薬理学会年会  公益社団法人日本薬理学会

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    Event date: 2014.3

    Language:English   Presentation type:Oral presentation (general)  

    Venue:仙台  

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  • Roles of the prostaglandin I2-IP system in nonalcoholic steatohepatisis International conference

    Kumei S., Yuhki K., Kojima F., Kashiwagi H., Okumura T., Narumiya S., Ushikubi F.

    第87回日本薬理学会年会  公益社団法人日本薬理学会

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    Event date: 2014.3

    Language:English   Presentation type:Oral presentation (general)  

    Venue:仙台  

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  • Thromboxane A(2) plays a critical role in reduction of the anti-platelet effect of prostaglandin I-2 receptor agonist beraprost after repeated administration

    Hitoshi Kashiwagi, Koh-ichi Yuhki, Fumiaki Kojima, Shima Kumei, Yoshiki Sakai, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2014  JAPANESE PHARMACOLOGICAL SOC

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    Event date: 2014

    Language:English  

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  • Roles of the prostaglandin I-2-IP system in nonalcoholic steatohepatitis

    Shima Kumei, Yuhki Koh-ichi, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2014  JAPANESE PHARMACOLOGICAL SOC

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    Event date: 2014

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  • Protective effect of the postaglandin I2-IP signal in MCD diet-induced nonalcoholic steatohepatitis in mice International conference

    Kumei S., Yuhki K., Kojima F., Kashiwagi H., Okumura T., Narumiya S., Ushikubi f

    Digestive Disease Week 

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    Event date: 2013.5

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Orlando  

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  • シスプラチン誘発急性腎障害におけるプロスタグランジンE2受容体サブタイプEP1の役割 International conference

    小島史章, 結城幸一, 柏木 仁, 粂井志麻, 成宮 周, 牛首文隆

    第86回日本薬理学会年会  日本薬理学会

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    Event date: 2013.3

    Language:English   Presentation type:Poster presentation  

    Venue:福岡  

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  • 非アルコール性脂肪性肝炎の発症・進展におけるプロスタグランジン I2 の役割解明 International conference

    粂井志麻, 結城幸一, 小島史章, 柏木 仁, 奥村利勝, 成宮 周, 牛首文隆

    第86回日本薬理学会年会  日本薬理学会

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    Event date: 2013.3

    Language:English   Presentation type:Oral presentation (general)  

    Venue:福岡  

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  • Roles of the prostaglandin I2-IP system in the development of nonalcoholic steatohepatitis. International conference

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JST-CREST 国際シンポジウム Frontiers in Immunology & I inflammation: From Molecules to Disease.  JST

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    Event date: 2013.2

    Language:English   Presentation type:Poster presentation  

    Venue:東京  

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  • 非アルコール性脂肪性肝炎の発症・進展におけるプロスタグランジンI2の役割解明

    粂井 志麻, 結城 幸一, 小島 史章, 柏木 仁, 奥村 利勝, 牛首 文隆

    日本薬理学雑誌  2013.1  (公社)日本薬理学会

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    Event date: 2013.1

    Language:Japanese  

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  • Role of the prostaglandin E-2 receptor subtype EP1 in cisplatin-induced nephrotoxicity

    Fumiaki Kojima, Koh-ichi Yuhki, Hitoshi Kashiwagi, Shima Kumei, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2013  JAPANESE PHARMACOLOGICAL SOC

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    Event date: 2013

    Language:English  

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  • Roles of the prostaglandin I-2-IP system in the development of nonalcoholic steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2013  JAPANESE PHARMACOLOGICAL SOC

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    Event date: 2013

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  • トロンボキサンA2合成酵素の阻害はプロスタグランジンI2受容体の脱感作を抑制する

    柏木 仁, 結城 幸一, 小島 史章, 酒井 芳紀, 牛首 文隆

    日本薬理学雑誌  2012.1  (公社)日本薬理学会

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    Event date: 2012.1

    Language:Japanese  

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  • 腎間質線維化におけるプロスタグランジンE2-EP4系の役割

    中川 直樹, 結城 幸一, 小島 史章, 柏木 仁, 藤野 貴行, 川辺 淳一, 長谷部 直幸, 牛首 文隆

    日本薬理学雑誌  2012.1  (公社)日本薬理学会

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    Event date: 2012.1

    Language:Japanese  

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  • Role of prostaglandin l(2) in nonalcoholic steatohepatitis

    Shima Kumei, Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Toshikatsu Okumura, Shu Narumiya, Fumitaka Ushikubi

    JOURNAL OF PHARMACOLOGICAL SCIENCES  2012  JAPANESE PHARMACOLOGICAL SOC

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    Event date: 2012

    Language:English  

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  • Facilitated progression of nonalcoholic steatohepatitis in mice lacking the prostaglandin I2 receptor International conference

    Kumei S., Yuhki K., Kojima F., Kashiwagi H., Okumura T., Narumiya S., Ushikubi F.

    Keystone Symposia 

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    Event date: 2011.5

    Language:English   Presentation type:Poster presentation  

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  • (シンポジウム「血管病の先端的研究と治療の新展開」) Roles of the prostanoids in the cardiovascular system.

    Yuhki K., Kawabe J., Takahata O., Hara A., Narumiya S., Ushikubi F.

    第79回日本薬理学会年会 

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    Event date: 2006.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:横浜  

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  • The prostaglandin E2-EP4 system protects the heart from ischemia-reperfusion injury. International conference

    Yuhki K., Xiao CY, Hara A., Fujino T., Narumiya S., Ushikubi F.

    12TH WORLD CONGRESS ON HEART DISEASE - NEW TRENDS IN RESEARCH, DIAGNOSIS AND TREATMENT 

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    Event date: 2005.7

    Language:English   Presentation type:Oral presentation (general)  

    Venue:CANADA  

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  • (シンポジウム「エイコサノイド -最近の知見-」) Roles of the prostanoids in the cardiovascular diseases.

    Yuhki K., Hara A., Narumiya S., Ushikubi F.

    第78回日本薬理学会年会 

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    Event date: 2005.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:横浜  

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  • 心筋の好気的エネルギー代謝障害による新しい心不全モデルの確立 : 新モデル動物の不全心筋におけるendothelin-1(ET-1)、atrial natriuretic peptide(ANP)mRNAの著明な発現増大とアポトーシスの存在

    村越,伸行, 宮内,卓, 柿沼,由彦, 結城,幸一, 酒井,俊, 山口,巖, 杉下,靖郎

    Japanese circulation journal  1999.3  Japanese Circulation Society

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    Event date: 1999.3

    Language:Japanese  

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  • 心臓でのendothelin(ET)-2の発現変化は、ET-1の発現変化と相反するパターンをとる。 : ET-2の不全心における発現低下と、培養心筋細胞での低酸素曝露に対する発現上昇

    柿沼,由彦, 後藤,勝年, 宮内,卓, 酒井,俊, 小林,勉, 下條,信威, 結城,幸一, 山口,巖, 杉下,靖郎

    Japanese circulation journal  1998.2  Japanese Circulation Society

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    Event date: 1998.2

    Language:Japanese  

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  • 低酸素応答における ETS 経路の役割

    結城幸一, 中山恒

    第75回日本薬理学会北部会  2024.9 

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  • ヒト血小板の機能調節におけるプロスタグランジンF2a の役割解明

    柏木仁, 結城幸一, 今道力敬, 粂井志麻, 小島史章, 成宮周, 牛首文隆

    第70回日本薬理学会北部会(札幌)  2019.9 

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  • 肝再生におけるプロスタグランジン I2-IP 系の役割

    平田朋浩, 結城幸一, 柏木仁, 今道力敬, 成宮周, 牛首文隆

    第70回日本薬理学会北部会(札幌)  2019.9 

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  • Concanavalin A 誘発肝炎におけるprostaglandin E2-EP4 系の役割

    今道力敬, 結城幸一, 柏木仁, 粂井志麻, 小島史章, 中西桂, 成宮周, 牛首文隆

    第92回日本薬理学会年会(大阪)  2019.3 

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  • マウス肝再生におけるプロスタグランジン I2 と TNF-a の役割

    結城幸一, 平田朋浩, 今道力敬, 柏木仁, 中山恒, 成宮周, 牛首文隆

    第94回日本薬理学会年会(札幌)  2021.3 

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  • 肝星細胞活性化におけるHIF-1a、HIF-2aの役割

    市川優花, 結城幸一, 中山恒

    北海道薬物作用談話会  2024.8 

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  • マウス肝再生におけるプロスタグランジンI2-IP 系の役割

    結城幸一, 平田朋浩, 今道力敬, 柏木仁, 成宮周, 牛首 文隆

    第93回日本薬理学会年会(横浜)  2020.3 

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  • プロスタグランジンE2-EP4 系は Concanavalin A 誘発肝炎において肝臓を保護する

    今道力敬, 結城幸一, 柏木仁, 粂井志麻, 中西桂, 小島史章, 成宮周, 牛首 文隆

    第93回日本薬理学会年会(横浜)  2020.3 

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  • クプリゾン誘発脱髄および運動機能障害における膜型プロスタグランジンE 合成酵素-1 の役割

    小島史章, 関谷広樹, 川田逸人, 柏木仁, 今道力敬, 結城幸一, 牛首文隆, 北里英郎, 市川尊文

    第93回日本薬理学会年会(横浜)  2020.3 

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Research Projects

  • プロスタグランジンD2の非アルコール性脂肪肝炎における役割の解明

    Grant number:19K07096  2019.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    結城 幸一, 今道 力敬

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    Grant amount:\4,160,000 ( Direct Cost: \3,200,000 、 Indirect Cost:\960,000 )

    非アルコール性脂肪肝炎(NASH)は、進行すると肝硬変や肝がんの発症リスクが高い。本邦において、NASH 患者は 200 万人以上と推定されているが、十分なエビデンスを持った薬物療法は未だ確立されていない。プロスタノイドは、プロスタグランジン(PG)とトロンボキサン(TX)より成る生理活性脂質であり、各プロスタノイドに特異的な受容体を介して非常に多彩な作用を示す。現在まで、PGD2、PGE2、PGF2α、PGI2、TXA2 の受容体として DP、EP、FP、IP、TP が知られている。本研究では、PGD2受容体DP欠損マウスと、高脂肪食負荷によりヒトNASHに近い表現型を示すメラノコルチン4受容体(MC4R)欠損マウスとを掛け合わせたMC4R/DPダブル欠損マウスを用いて解析を行う。前年度、ウェスタンダイエット後に少量の四塩化炭素を投与することによってNASH様病態を呈する短期NASHモデルを使った解析で、四塩化炭素投与1日目の血中トランスアミナーゼ量がMC4R欠損マウスよりMC4R/DPダブル欠損マウスで低値を示し、肝組織における線維化関連因子のmRNA発現も低値を示し知見を得ていた。今年度、この短期NASHモデルを用い、RNA-Seqを行い、PGD2-DP系がどのような因子の発現に関与しているのか詳細に解析する予定であった。しかし、マウスへのウェスタンダイエットがうまくいかず、サンプルを得ることが出来なかった。一方、肝線維化において中心的な役割をしている肝星細胞をマウスより単離培養し、TGF-beta刺激による線維化関連因子の発現変動へのPGD2の役割を解析したが、PGD2による発現抑制作用は認められなかった。今後、刺激因子や培養条件を変えてさらに解析する予定である。

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  • Elucidation of the role of prostanoids in the development of liver fibrosis

    Grant number:18H02576  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Ushikubi Fumitaka

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    Grant amount:\17,290,000 ( Direct Cost: \13,300,000 、 Indirect Cost:\3,990,000 )

    To elucidate the role of prostanoids in liver fibrosis, we analyzed several animal models of non-alcoholic steatohepatitis (NASH) using prostanoid receptor-deficient mice. In this study, prostaglandin (PG) I2 was suggested to suppress liver fibrosis and PGF2α to promote liver fibrosis during the development of NASH. An analysis using a microarray, however, indicated that the stimulation of FP, which is a receptor for PGF2α, enhances not only the factors promoting hepatic fibrosis but also the factors suppressing hepatic fibrosis.

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  • Regulation of cardiac prostanoid synthesis by glucocorticoid and its pathophysiological meaning

    Grant number:25670124  2013.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    USHIKUBI Fumitaka, YUHKI Koh-ichi, KASHIWAGI Hitoshi

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    Grant amount:\3,900,000 ( Direct Cost: \3,000,000 、 Indirect Cost:\900,000 )

    Recently, glucocorticoid has been reported to up-regulate cardiac prostanoid synthesis. However, the precise mechanism of this regulation remains to be clarified. On the other hand, the prostanoids play an important role in the pathogenesis of acute myocardial infarction and pressure overload-induced cardiac hypertrophy. The aims of this study are to clarify the regulatory action of glucocorticoid on cardiac prostanoid synthesis and its role in the pathogenesis of cardiac diseases. Glucocorticoid induced up-regulation of COX-1 and L-PGDS, the enzymes for prostanoid biosynthesis, and prostanoid receptors FP and EP2 in the heart. Because we established the murine model of adrenal ablation, we would like to examine the pathophysiology of these mice subjected to cardiac infarction or cardiac pressure overload.

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  • The elucidation of the signal transduction system of ischemic myocardial protection of prostanoids

    Grant number:23590294  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YUHKI KOH-ICHI

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    Grant amount:\5,330,000 ( Direct Cost: \4,100,000 、 Indirect Cost:\1,230,000 )

    After the onset of myocardial infarction, timely myocardial reperfusion is essential for myocardial salvage. However, reperfusion itself exacerbates injury of previously ischemic myocardium. (reperfusion injury). The excessive release of norepinephrine from cardiac sympathetic nerve terminal is known to be involved in the pathogenesis of ischemic cardiac injury. Prostanoids are bioactive lipid mediators consisting of prostaglandins (PGs) and thromboxane. In this research, we analyzed the mechanism of the cardioprotective action of prostanoids in myocardial infarction, using mice lacking the PGE2 receptors. In ischemic hearts, we demonstrated that endogenous PGE2 suppresses norepinephrine release via EP3 receptor.

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  • Roles of the prostanoids in the regulation of immunological responses

    Grant number:23659130  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    USHIKUBI Fumitaka, YUHKI Koh-ichi, KASHIWAGI Hitoshi

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    Grant amount:\3,770,000 ( Direct Cost: \2,900,000 、 Indirect Cost:\870,000 )

    To clarify the roles of the prostanoids in the regulation of immunological responses, we employed two animal models showing pathophysiology dependent on immunological responses; renal interstitial fibrosis and Con A-induced hepatitis. Through the analysis of these animal models, we found novel roles and action mechanisms of the PGE2-EP4 system in the development of renal interstitial fibrosis and Con A-induced hepatitis._4

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  • Roles of the prostanoids in the pathogenesis of cardiovascular diseases

    Grant number:22390045  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    USHIKUBI Fumitaka, KOJIMA Fumiaki, KASHIWAGI Hitoshi, YUHKI Koh-ichi

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    Grant amount:\18,590,000 ( Direct Cost: \14,300,000 、 Indirect Cost:\4,290,000 )

    To clarify the roles of the prostanoids in the cardiovascular system, we employed several animal models showing similar pathophysiology with those seen in human diseases. Through the analysis of these animal models, we found novel actions of the prostanoids, which include the role of the EP4 and IP in the development of renal interstitial fibrosis, the role of the EP1 in the development of cisplatin-induced nephropathy and the potent inhibitory action of ONO1301 on platelet aggregation._4 Au

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  • Role of prostanoids in the bone marrow derived endothelial cells

    Grant number:22590765  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    OKADA Motoi, KAWABE Junichi, YUHKI Kouiti

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    Grant amount:\2,860,000 ( Direct Cost: \2,200,000 、 Indirect Cost:\660,000 )

    We clarified the role of vascular prostanoids, i.e. prostacyclin and thromboxane in the bone marrow-derived endothelial cells (EPC). EPC expressed their specific receptor, IP and TP respectively. We observed the functional changed of EPCs derived from IP- or TP-deleted mice using injured femoral artery vascular remodeling and peripheral ischemic models. Finally we found that PGI2 and TXA2 strictly regulated the function of EPCs and contribute to the pathogenesis of vascular diseases.

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  • The mechanism elucidation of the protective effect of prostanoids in ischemic myocardial protection

    Grant number:20590244  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YUHKI Koh-Ichi

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    Grant amount:\4,810,000 ( Direct Cost: \3,700,000 、 Indirect Cost:\1,110,000 )

    Prostanoids are bioactive lipid mediators consisting of prostaglandins (PGs) and thromboxanes. On the other hand, Ischemic preconditioning (IPC) is a phenomenon that a brief ischemia of the heart induces a potent cardioprotective mechanism upon a succeeding ischemic insult. This research was analyzed about the roles of prostanoids in the ischemic heart disease using mice lacking PGE_2 receptor. We demonstrated that the PGE_2-EP_4 system exerts the cardio-protective effect in the late phase of IPC partly by augmenting the anti-apoptosis related signaling.

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  • Roles of prostanoids in the pathogenesis of cardiovascular diseases

    Grant number:19390060  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    USHIKUBI Fumitaka, YUHKI Koh-ichi, SUZUKI Yasuhiro

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    Grant amount:\18,460,000 ( Direct Cost: \14,200,000 、 Indirect Cost:\4,260,000 )

    We intended to clarify the roles of prostanoids in the pathogenesis of cardiovascular diseases using mice lacking each prostanoid receptor and murine model of cardiovascular diseases. We clarified the cardioprotective effect of PGE_2 and the suppressive effect of PGI_2 on vascular remodeling. We also found an anti-platelet effect of PGE_2 via EP4 receptor.

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  • A study of the roles of prostanoids and its therapeutic application in cardiovascular remodeling

    Grant number:18590229  2006 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HARA Akiyoshi, USHIKUBI Fumitaka, YUHKI Koh-ichi, HANAKAI Takahiro, KONDO Yuhki, YANAGISAWA Terufumi

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    Grant amount:\4,190,000 ( Direct Cost: \3,500,000 、 Indirect Cost:\690,000 )

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  • Roles of the prostanoids in the myocardial infarction and application to the treatment

    Grant number:17590211  2005 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YUHKI Koh-Ichi

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    Grant amount:\3,800,000 ( Direct Cost: \3,500,000 、 Indirect Cost:\300,000 )

    Prostanoids, the prostaglandin (PGs) and thromboxane (TXs), are the cyclooxygenase metabolites of arachidonic acids and exert a range of actions in the body. These actions are mediated by their respective receptors expressed in the targe cells, which are generally present in the vicinity of prostanoid production. The receptors include the DP, EP, FP, IP and TP respectively. Moreover, there are four subtypes of the EPs: EP_1, EP_2 EP_3, and EP_4. The PGE_2, the common prostanoid in the cardiovascular system, is produced during cardiac ischemia/reperfusion (I/R). We intended to clarify the roles of PGE_2 in cardiac I/R injury using mice lacking the PGE_2 receptor EP_1, EP_2, or EP_3. Mice were subjected to coronary occlusion followed by reperfusion.
    Myocardial infarct size in EP_3^<-/-> mice was significantly larger than that in wild-type (WT) mice. In contrast, there was no such difference among EP_1^<-/->, EP_2^<-/-> and WT mice. To further determine whether PGE_2 acts directly on the heart or indirectly through their action on blood constituents, we examined I/R injury ex vivo. Excised hearts were perfused according to Langendorff technique and were subjected to I/R. In EP_3^<-/-> mice, developed pressure during reperfusion was significantly lower, and release of creatine kinase was significantly augmented than those in WT mice. These results indicate the possibility that endogenous PGE_2 acts on the EP_3 in the heart and plays a cardioprotection role in I/R injury. In in vivo study, when the EP_3 agonist was administered 1 hour before coronary occlusion, it reduced infarct size significantly in wild-type mice. The potent cardioprotective effects of the EP_3 agonist suggest that the compound would be useful for treatment of acute myocardial infarction.

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  • A study of roles of the prostanoids in cardiovascular remodeling using mice lacking deficient in prostanoid receptors

    Grant number:15590265  2003 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HARA Akiyoshi, YUHKI Koichi

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    Grant amount:\3,600,000 ( Direct Cost: \3,600,000 )

    In the heart, the expressions of several types of prostanoid receptors have been reported. However, their roles in cardiac hypertrophy in vivo remain unknown. We intended to clarify the roles of these receptors in pressure overload-induced cardiac hypertrophy using mice lacking each of their receptors. We employed a model of pressure overload-induced cardiac hypertrophy produced by banding of the transverse aorta in female mice. In wild-type mice subjected to the banding, cardiac hypertrophy developed during the observation period of 8 weeks. In mice lacking the prostaglandin (PG) I_2 receptor (IP^<-/-> mice), however, cardiac hypertrophy and cardiomyocyte hypertrophy were significantly greater than in wild-type mice at 2 and 4 weeks but not at 8 weeks, while there was no such augmentation in mice lacking the prostanoid receptors other than IP. In addition, cardiac fibrosis observed in wild-type hearts was augmented in IP^<-/-> hearts, which persisted for up to 8 weeks. In IP^<-/-> hearts, the expression level of mRNA for atrial natriuretic peptide, a representative marker of cardiac hypertrophy, was significantly higher than in wild-type hearts. In vitro, cicaprost, an IP agonist, reduced platelet derived growth factor-induced proliferation of wild-type non cardiomyocytes, although it could not inhibit cardiotrophin-1-induced hypertrophy of cardiomyocytes. Accordingly, cicaprost increased cAMP concentratiion efficiently in noncardiomyocytes. The results indicate that IP plays a suppressive role in the development of pressure overload-induced cardiac hypertrophy via the inhibition of both cardiomyocyte hypertrophy and cardiac fibrosis, both effects having been suggested as originating from the action on non-cardiomyocytes rather than that on cardiomyocytes.

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  • 受容体欠損マウスを用いた虚血-再灌流障害におけるプロスタグランジンE_2の役割解明

    Grant number:15790374  2003 - 2004

    日本学術振興会  科学研究費助成事業  若手研究(B)

    結城 幸一

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    Grant amount:\3,500,000 ( Direct Cost: \3,500,000 )

    本研究の目的は、虚血-再灌流障害におけるプロスタグランジン(PG)E_2の役割を受容体欠損マウスを用いて解明することであった。本研究によって、以下のことが明らかになった。虚血-再灌流障害のモデルを用い、in vivoとex vivoの実験を行った。in vivoの実験では、マウスの左冠動脈前下行枝を1時間結紮し、その後、24時間再灌流を行い、梗塞サイズを測定した。この結果、心筋梗塞サイズは、野生型と比較してPGE_2受容体の一つであるEP_4の欠損マウスにおいて著しい増加を認めた。つまり、心筋の虚血-再灌流障害に対して内因性PGE_2は、EP_4を介して心筋保護に働くことを初めて明らかにした。ex vivoの実験では、摘出灌流心への灌流液の供給を遮断し、その後再灌流を行い、心機能の変化を解析した。その結果、野生型マウスに比較し、EP_4欠損マウスでは、再灌流時のdeveloped tensionの回復が抑制され、CK遊出量は高値を示した。つまり、内因性PGE_2の心筋保護作用には、EP_4を介した心臓への直接作用も含まれていることが初めて明らかとなった。さらに、野生型マウスに対し、虚血前、あるいは虚血中に選択的EP_4アゴニストを投与し、その後再灌流を行い、24時間後に心臓の梗塞サイズを解析した。その結果、虚血前、虚血中のいずれの投与においても、EP_4アゴニストは梗塞サイズの有意な低下を引き起こした。この効果は、EP_4欠損マウスにおいて完全に消失した。よって、外因性に投与したEP_4アゴニストは、EP_4を介して虚血心筋保護に働くことを初めて明らかにした。また、EP_3欠損マウスについても解析を行った結果、内因性PGE_2がEP_3を介した心臓保護作用も有することが明らかとなった。

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  • Roles of prostanoids in cardiovascular system revealed from studies using knockout mice

    Grant number:14370049  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    USHIKUBI Fumitaka, HARA Akiyoshi, YUHKI Koh-ichi

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    Grant amount:\14,700,000 ( Direct Cost: \14,700,000 )

    The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attmpted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for pressure overload-induced cardiac hypertrophy and renovascular hypertention, and in vitro systems such as for cultures of cardiomyocytes from fetal or adult mice and culture of juxtagromerullar cells. We next examined the roles of the prostanoids using the established methods and knockout mice. Prostaglandin (PG) I_2 was found to be a potent inhibitor of cardiac hypertrophy consisting of cardiomyocyte hypertrophy and cardiac fibrosis via its receptor IP. PGI_2 playd an important pathophysiological role in the development of renovascular hypertension. This role was attained by the stimulation of the renin-angiotensine-aldosterone system by PGI_2. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles of the prostanoids in various pathological conditions such as cardiac ischemia-reperfusion injury, vascular remodeling and inflammatory tachycardia.

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  • プロスタノイドの肝機能障害・肝再生におけるプロスタノイドの役割解明

    Grant number:14657036  2002 - 2003

    日本学術振興会  科学研究費助成事業  萌芽研究

    牛首 文隆, 結城 幸一

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    Grant amount:\3,200,000 ( Direct Cost: \3,200,000 )

    本研究の目的は、肝機能障害や肝再生におけるプロスタノイドの生理的・病態生理的役割を解明することであった。2年間の研究によって以下のことが明らかとなった。
    1.正常マウス肝臓におけるプロスタノイド受容体の発現についてRT-PCR法により確認した。その結果、8種類のプロスタノイド受容体の中で、EP_2、EP_3、EP_4、FP、IP、TPの6種類の発現を確認した。さらに、マウス肝臓をコラゲナーゼで灌流し、低速遠心することによって多種類の細胞から構成される肝臓より肝実質細胞のみを単離し、プロスタノイド受容体mRNAの発現を調べた。その結果、EP_3、EP_4、FP、IP、TPの5種類の発現を確認したが、肝組織では検出されたEP_2が肝実質細胞では検出されなかった。
    2.肝機能障害におけるプロスタノイドの関与を調べるために、四塩化炭素を投与し、その後、12時間ごとに肝組織で発現が確認されたプロスタグランジン(PG)E_2の受容体であるEP_2、EP_3、EP_4のそれぞれに対する特異的アゴニストを投与した。その結果、四塩化炭素投与によって生じる組織傷害の指標である血中LDHやALTの上昇がEP_4アゴニスト投与によって有意に低下した。また、四塩化炭素投与48時間後に肝臓の組織切片を作成し、Necrotic areaを解析した。その結果、EP_4特異的アゴニスト投与群において、コントロールと比較して有意なNecrotic areaの低下が認められた。この作用は、EP_4欠損マウスを用いたところ完全に消失した。つまり、PGE_2は、EP_4を介して肝細胞障害に対し、細胞保護に働くことが明らかとなった。

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  • 心肥大・心不全における内因性プロスタノイドの役割の解明

    Grant number:13770338  2001 - 2002

    日本学術振興会  科学研究費助成事業  若手研究(B)

    結城 幸一

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    Grant amount:\2,300,000 ( Direct Cost: \2,300,000 )

    本研究の目的は、心肥大・心不全におけるプロスタノイドの役割を受容体欠損マウスを用いて解明することである。本研究によって、以下のことを明らかにした。
    1.心臓におけるプロスタノイド受容体の発現をRT-PCRにより解析した。成獣マウス心室筋では、8種類のプロスタノイド受容体の中で、EP_2、EP_3、EP_4、FP、IP、TPの発現を確認した。さらに、心室から単離した成獣および胎仔心筋細胞では、EP_2を除いた5種類の発現を確認した。また、胎仔非心筋細胞では、成獣心室と同様に6種類の受容体が発現していることを明らかにした。
    2.トロンボキサン(TX)A_2は、非心筋細胞の増殖を促進した。この作用は、TP欠損マウスでは消失した。よって、TXA_2は、TPを介して、非心筋細胞の増殖を促進することが明らかとなった。
    3.急性心不全のモデルとして、虚血-再灌流障害のin vivoとex vivoの実験を行った。in vivoの実験では、左冠動脈を1時間結紮し、その後、再灌流を24時間行い、梗塞サイズを測定した。この結果、心筋梗塞サイズは野生型と比較してIP欠損マウスにおいて著しい増加を認めた。つまり、心筋の虚血-再灌流障害に対して、内因性PGI_2はIPを介して心筋保護に働くことを初めて明らかにした。ex vivoの実験では、摘出灌流心への灌流液の供給を遮断し、その後再灌流を行い、心機能の変化を解析した。その結果、野生型マウスに比較し、IP欠損マウスでは、再灌流時のdeveloped tensionの回復が抑制され、CK遊出量は高値を、ATP含量は低値を示した。つまり、内因性PGI_2の心筋保護作用には、IPを介した心臓への直接作用も含まれていることが初めて明らかとなった。

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  • 心不全の心筋におけるエンドセリン産生の転写調節機構に関する分子生物学的研究

    Grant number:11770346  1999 - 2000

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    結城 幸一

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    Grant amount:\2,100,000 ( Direct Cost: \2,100,000 )

    本研究の目的は、心不全のような慢性期の病態におけるエンドセリン(ET)-1産生のメカニズムを明らかにすることである。我々は心不全という病態が、その一側面では心筋のエネルギー代謝不全であることに着目した。心不全において、心筋のエネルギー産生系はミトコンドリアにおける脂肪酸のβ酸化から解糖系にシフトしている。この解糖系の遺伝子の発現を制御している転写因子の一つとしてhypoxia inducible factor(HIF)-1αがある。本研究はHIF-1αとET-1との関係について調べ、以下のことを明らかにした。
    1.2つの心不全モデル動物を用いて遺伝子発現の変化を経時的に調べた。その結果、HIF-1αの遺伝子発現はET-1の遺伝子発現と相関して、心不全の進行と共に増加した。
    2.ET-1の5'非翻訳領域には、HIF-1αの認識配列が存在する。HIF-1α及びET-1の5'非翻訳領域を組み込んだプラスミドを用いて、ルシフェラーゼアッセイを行った。その結果、HIF-1αはET-1の5'非翻訳領域を認識してET-1の遺伝子発現を増加した。
    3.HIF-1αとET-1の翻訳調節領域との結合を確認するために、ゲルシフトアッセイをおこなった。その結果、心筋細胞内のHIF-1α蛋白質とET-1の5'非翻訳領域のオリゴヌクレオチドとの結合が認められた。
    4.心筋のエネルギー代謝不全によってET-1の遺伝子発現が上昇するか、培養心筋細胞を使って調べた。ミトコンドリアの機能を障害した時、HIF-1αとET-1の遺伝子発現は顕著に増大した。この時、HIF-1αのアンチセンスオリゴヌクレオチドの添加は、ET-1の遺伝子発現増大を抑制した。これらの結果は、心不全においてエネルギー代謝不全を補うためにHIF-1αが誘導され、これがET-1の産生増大の一部を担っていることが示された。

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  • Response of Cardiomyocyte to Cellular Injury

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  • 循環器系におけるプロスタノイドの役割の解明

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  • Clarification of roles of prostanoids in cardiovascular system

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  • 心筋細胞の細胞障害に対する応答調節について

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    旭川ウェルビーイング・コンソーシアム、旭川市  2025.6

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    2023.7

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    2022.7

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    2021.8

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    「体験!2019年ノーベル賞研究
    ~生物が酸素を感知するしくみを知ろう~」
    細胞が持つ酸素を感知する仕組みを、培養細胞などを使って観察する。

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    2016.8

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    実習に先立ち、高校生および引率教諭へ動物実験の必要性などの講義をおこなった。
    高校生へ実験動物の解剖法などを教えた。

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    The American Society for Pharmacology and Experimental Therapeutics  2025.3

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  • 第96回日本薬理学会年会座長 International contribution

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    2022.11 - 2022.12

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    2022.11 - 2022.12

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    2021.8 - 2022.12

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    2021.3

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    2020.11 - 2025.3

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    日本薬理学会  2020.8 - 2021.3

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  • 第69回日本薬理学会北部会シンポジウムオーガナイザー

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    2012.9

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    2009.3

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    2008.9

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    2007.9

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    日本薬理学会  2007.4

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    2005.4

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