| Project/Area Number |
24591201
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ABE Hideharu 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (60399342)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Naoko 徳島大学, 病院, 特任助教 (70623271)
KISHI Seiji 徳島大学, 病院, 助教 (10519507)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 慢性腎臓病 / 細胞老化 / 加齢 / Smad1 / ネフロン / CKD / 腎機能低下 / ネフロン数 / BMP4 |
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| Outline of Final Research Achievements |
It seems likely with the increases in the incidence of diabetes, vascular disease, and the general aging of the population that the true prevalence of CKD has increased, but it is very hard to make a precise diagnosis and predict the prognosis. Molecular mechanisms leading to nephron loss with normal aging or with aging accompnying some CKD remains unknown. We previously Smad1 plays a critical role for the initiation of glomerulosclerosis. Mesangial cells isolated from Smad1 transgenic mice exhibit typical changes of cellular senescence. Since E12 proteins induce p21waf1/cip1 under non-diabtic conditions and thereby promote cellular sensescence. We conducted to screen E12-binding proteins using Y2H method and found Flash (casp8ap2) protein. Flash critically suppress TNFalpha-p21-dependent cellular senescence in a p53-indpendent manner. Moreover, high dose of TNFalpha induces Flash expression in parallel with a decrease of p21waf1/cip1. Collectively, Flash might be a therapeutic target.
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