| Project/Area Number |
18591183
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SEKINE Takashi The University of Tokyo, Dept of Pediatrics, Graduate Scholl of Medicine, Associate Professor (50255402)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Takashi The University of Tokyou, Dept of Pediatrics, Graduate School of Medicine, Professor (70151256)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Neph1 / nephrin / phosphorylation / PAN nephrosis model / TRPC6 / PLC_γ / Caチャネル活性 / 蛋白尿 / 糸球体上皮細胞 / スリット膜 / 質量分析 / シグナル伝達 |
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| Research Abstract |
In the present study, at first, we identified the phosphorylation of npeh1, which consists of slit membrane of glimerular podocyte. In addition, we determined the tyrosine residues, which are phosphorylated in protamine sulfate and PAN nephrosis model animals.
In the second year, we performed the analysis of signal transduction in podocyte after tyrosine phosphorylation of neph1 and nephrin. The following two points are critical.
1. Neph1, PLCγ and TRPC constitute molecular complex in podocyte.
2. Function of TRPC6 is regulated by phosphorylatiion of nephrin.
TRPC6 is a molecule, whose genetic mutations induce human hereditary nephritic syndrome. The fact that neph1, PLCγ and TRPC constitute molecular complex in podocyte strongly suggest that the phosphorylation of neph1 is associated with the development of nephritic syndrome.
Furthermore, regulation of TRPC6 channel by nphrin phosphorylation also suggests its critical role in nephrosis.
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