Organization
Hospital Clinical Departments Pediatrics
External link
ISHIBAZAWA Emi
Research Projects
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Research for the Pathological Understanding and Therapeutic Development of SIFD Using iPS Cells
Grant number：24K11037 2024.4 - 2027.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Grant amount：\4,680,000 （ Direct Cost: \3,600,000 、 Indirect Cost：\1,080,000 ）
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リポソームを捕捉したマクロファージのMDSC様細胞への変容に関わる分子基盤の解明
Grant number：23K07243 2023.4 - 2026.3
日本学術振興会 科学研究費助成事業 基盤研究(C)
吉田 陽一郎, 東 寛, 佐藤 雅之, 甲賀 大輔, 長森 恒久, 青山 藍子, 酒井 宏水, 石羽澤 映美
Grant amount：\4,160,000 （ Direct Cost: \3,200,000 、 Indirect Cost：\960,000 ）
A)リポソーム捕捉マクロファージの表現型解析
RAW264.3細胞にリポソームを添加した際に、まず細胞内シグナル伝達に関して、添加後1時間後からIkBaの減少、リン酸化ERK、p38MAPK、JNKの増加を見た。サイトカイン分泌に関してはリポソームを添加した際にIL-6,TNFなどの向炎症性サイトカインのごく少量の増加を見た。また、iNOSと、免疫チェックポイント分子の発現量をフローサイトで解析し、リポソーム添加後12時間以降にiNOS、及びPD-L1の発現増加を確認した。
これらは先行するラットでのex vivo研究と共通するもので、リポソーム捕捉マクロファージのMDSC様変容と合致する所見であった。 -
TRNT1 functional analysis for the Pathological Understanding of SIFD
Grant number：21K07836 2021.4 - 2024.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Nagamori Tsunehisa
Grant amount：\4,290,000 （ Direct Cost: \3,300,000 、 Indirect Cost：\990,000 ）
During study period, the following findings were made:
1. In PBMC of the patient, TRNT1 was expressed at a lower level than in healthy individuals, even though it was the same size.This was due to its constant degradation by the proteasome because of its instability.2.Patient fibroblasts exhibited increased drug-induced endoplasmic reticulum (ER) stress compared to healthy fibroblasts.3.TRNT1 siRNA knockdown in immortalized fibroblasts also showed increased ER stress, which was alleviated by the chemical chaperone 4-phenylbutyric acid. 4.When TRNT1 was knocked down in mouse macrophage-like Raw cells, there was an increase in TNF production and NF-kB signaling.
From the above, it was suggested that in SIFD (Sideroblastic Anemia with B-cell Immunodeficiency, Periodic Fevers, and Developmental Delay), enhanced ER stress response occurs, which is likely involved in the pathogenesis of the disease.