| Co-Investigator(Kenkyū-buntansha) |
ORIKASA Michiaki Faculty of Medicine, Niigata University, Professor, 医学部, 教授 (30185681)
SHIMIZU Fujio Faculty of Medicine, Niigata University, Professor, 医学部, 教授 (40012728)
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| Research Abstract |
In this project, we analyzed the function of the slit diaphragm for maintaining the barrier function of the glomerular capillary wall. We obtained the following findings ; (1) Nephritogenic monoclonal antibody 5-1-6 recognizes the extracellular site of nephrin, a gene product of NPHS1. (2) Nephrin is a component of the slit diaphragm. (3) Nephrin expression is decreased in several proteinuric states. (4) Nephrin is essential for maintaining the barrier function of the slit diaphragm, but not essential for maintaining the structure of the slit diaphragm. (5) In proteinuric states, not only nephrin but also podocin, a gene product of NPHS2 and ZO-1 decrease. We obtained these results with fat experimental models. We cloned rat homologues of nephrin and podocin (GenBank AF161715, AY039651), since cloning of rat homologue is indispensable for investigation with rat model. We also investigated the developmental mechanism of nephrin and podocin. In addition, we obtained the important finding that the decreased expression of nephrin was a critical factor for the development of the irreversible mesangial alterations. These findings were reported at the annual meetings of American Society of Nephrology and Japanese Society of Nephrology 1999, 2000, 2001 and were published in Kidney International 2000 May and 2001 December and other journals. A series of the studies in this project clearly indicated that proper arrangement of nephrin, ZO-1 and podocin were essential for maintaining the barrier function of the slit diaphragm.
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