Project/Area Number |
19390281
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | The University of Tokyo |
Principal Investigator |
IGARASHI Takashi The University of Tokyo, 医学部附属病院, 教授 (70151256)
|
Co-Investigator(Kenkyū-buntansha) |
SEKINE Takashi 東邦大学, 医学部附属病院・大橋病院, 教授 (50255402)
張田 豊 横浜市立大学, 生命ナノシステム科学研究科, 特任助教 (10451866)
|
Co-Investigator(Renkei-kenkyūsha) |
HARITA Yutaka 横浜市立大学, 生命ナノシステム科学研究科, 特任助教 (10451866)
|
Project Period (FY) |
2007 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2009: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
|
Keywords | ネフローゼ症候群 / 蛋白尿 / プロテオミクス / 腎臓 / 糸球体上皮細胞 / Nephrin / TRPC6 / MYN9 / Epstein-Fechtner症候群 / プロテオーム / ネフローゼ / 細胞内情報伝達 / ネフリン / ポドサイト |
Research Abstract |
A specialized intercellular junction between podocytes, known as the slit diaphragm, forms the essential structural framework for glomerular filtration in the kidney. In this study, we performed proteomic analysis to characterize the structure and function of slit diaphragm as a signaling complex. We found that post-translational modification orchestrates a wide spectrum of protein-protein interactions and intracellular signaling networks at slit diaphragm. These results unraveled the role of dynamics of slit diaphragm signal complex in modulating the glomerular filtration barrier function. We also performed genetic studies on Epstein and Fechtner syndromes which often develops progressive nephrotic syndrome, and found that R702 mutations display a strict genotype-phenotype correlation, and lead to the rapid deterioration of podocyte structure. Our results highlight the critical role of functional podocyte molecules in the development of Nephrotic syndrome.
|