| Project/Area Number |
19K17745
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
Seiji Kishi 川崎医科大学, 医学部, 准教授 (10519507)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 線維化 / DNA損傷 / 細胞老化 / 腎臓病 / TASCC / DNA損傷応答 / mTOR-オートファジー共存コンパートメント / AKI to CKD transition / 慢性腎臓病(CKD) / DNA障害 |
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| Outline of Research at the Start |
急性腎障害が慢性腎臓病に移行する過程のメカニズム解明は、不可逆的に進行し、腎臓病予後と直接関係する腎臓間質線維化の制御に繋がる。申請者はこの領域を世界的にリードするHarvard大学、Brigham and Women's病院のBonventre Labに留学し、この領域の研究を開始した。虚血、感染症、薬剤などによる種々の刺激によって障害を受けた結果、不全修復に陥った近位尿細管上皮細胞の細胞周期G2/M でのアレストと細胞レベルでの老化の関係、さらには細胞老化が不可逆的臓器機能低下に繋がる組織の線維化を進めるに至る分子機構を詳細に明らかにして腎臓病治療法開発を目指す。
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| Outline of Final Research Achievements |
The proximal tubules, which make up a significant portion of the kidney, are susceptible to various intrinsic and extrinsic factors that can lead to impairment. They play a central role in the fibrosis of the renal interstitium, which determines renal prognosis. The applicant focused on DNA damage and repair mechanisms in the proximal tubules caused by various intrinsic stresses, particularly in relation to cellular senescence, which is closely associated with DNA damage. The applicant conducted research using genetically modified animals to analyze these relationships. In mice with severe fibrosis in the tubulointerstitium, there was an increase in DNA damage that accelerated renal aging. The proximal tubules showed the formation of a cellular organelle complex called TASCC.
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| Academic Significance and Societal Importance of the Research Achievements |
老化細胞を除去することで臓器機能を改善したり、生命延長ができることも近年明らかになってきた。したがって、腎の細胞老化を制御して腎不全治療ができる可能性を高める研究成果を提供できることになる。
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