| Project/Area Number |
21790808
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
ARAI Hidenori 京都大学, 医学研究科, 教授 (60232021)
ABE Hideharu 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60399342)
DOI Toshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60183498)
IEHARA Noriyuki 京都大学, 医学研究科, 助教 (20281727)
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| Research Collaborator |
NAGAI Kojiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
MIMA Akira 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 老化 / 細胞・組織 / 病理学 |
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| Research Abstract |
Glomerulosclerosis is the most common cause of chronic renal failure in aging. It is pathologically characterized by the accumulation of extracellular matrix in mesangium, of which main component is type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic condition in vitro. To elucidate the mechanism of glomerulosclerosis in aging, we addressed the role of Smad1 in glomerulosclerosis during diabetes. First, we showed overexpression of Smad1 exacerbates glomerulosclerosis in diabetic mice, and identified bone morphogenetic protein 4 (BMP4) as a potent stimulator of Smad1 during diabetes. Now we are checking the role of BMP4 for biological aging process. Id (Inhibitor of differentiation), one of the important transcriptional factors regulated by Smad1, is known to inhibit basic-helix loop helix protein such as E2A, and to regulate cellular senescence. We showed that PIASy, which was also identified as a regulator of cellular senescence, is also a novel E2A binding partner, and enhances its sumoylation as a specific SUMO-E3 ligase, leading to down-regulate phenotypic changes of mesangial cells.
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