| Project/Area Number |
14370317
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
KAWACHI Hiroshi Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60242400)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Fujio Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40012728)
KOIKE Hiroko Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (90323964)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | proteinuria / podocyte / slit diaphragm / nephrin / podocin / NEPH1 / CD2AP / IP-10 |
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| Research Abstract |
Our group has been studying the molecular composition of slit diaphragm(SD) of podocyte that is accepted to be a critical structure for maintaining the barrier function of glomerular capillary wall. In this project, we analyzed the molecular composition of the SD. In the first year of this project (2002), we analyzed the nature of the SD-associated molecules, podocin, CD2AP and ZO-1. In the second year (2003), we cloned a rat homologue of NEPH1 and analyzed its molecular nature. In the final year (2004), we analyzed the interaction of these SD associated molecules with nephrin. In addition, we tried to identify other important molecules of the SD. We detected that podocin is expressed not only in podocyte but also in astrocyte in brain, which suggested that podocin play a role in regulating the function of blood-brain barrier as well as in glomerular capillary wall. We observed that the expression of podocin, CD2AP, ZO-1, and NEPH1 is altered in proteinuric states. We showed that the interactions of nephrin-podocin and nephrin-CD2AP are dissociated at the onset of proteinuria. We also demonstrated that interferon-inducible protein 10 is expressed in podocyte and play a role in regulating the expression of the SD-associated molecules. We published these findings as manuscripts in the top journals of Nephrology field, Kidney International and Journal of American Society of Nephrology. We reported some results at the annual meeting of the American Society of Nephrology held in San Diego (2003) and St.Rouis (2004). We are convinced that the results obtained in this project contributed to the better understanding the pathogenic mechanism of proteinuria and to establishment for the novel therapy.
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