| Project/Area Number |
07457239
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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 | UNIVERSITY OF TOKYO |
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Principal Investigator |
WATANABE Tsuyoshi University of Tokyo, Faculty of medicine, Associate professor, 医学部・附属病院, 助教授 (80158641)
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| Co-Investigator(Kenkyū-buntansha) |
東郷 真子 東京大学, 保健センター, 医員
SEKI George University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (30206619)
TANIGUCHI Shigeo University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (50188380)
NAKAO Akihide University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (10159056)
HASHIMOTO Yoshiaki University of Tokyo, Faculty of medicine, Lecturer, 医学部・附属病院, 講師 (40172879)
TOGO Masako University of Tokyo, Faculty of medicine, Senior Resident
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| Project Period (FY) |
1995 – 1996
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| Keywords | platelet-activating factor receptor / thromboxane A_2 receptor / microdissection / nephron / RT-PCR / mRNA expression / glomerular mesangial cells / homologous down-regulation |
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| Research Abstract |
In order to clarify the action mechanisms and physiological and pathophysiological significances of lipid autacoids such as platelet activating factor (PAF) and thromboxane (TX) A_2, we performed molecular and cellular biological studies in microdissected nephron segments from rodent kidneys, cultured renel-derived cells such as glomerular mesangial cells, genetically target mouse and DNA samples from patients with renal diseases, the results of which are as follows ; (1) Using our new quantitative RT-PCR method (MRT-PCR) in microdissected segments, we demonstrated ubiquitous distribution of PAF and TXA_2 receptor mRNA in the nephron, (2) homologous down-regulation of PAF receptor mRNA expression was shown to be mediated by cAMP formed though PAF-induced PGE_2 production in cultured mesangial cells, (3) pathophysilogical contribution of PAF on the pathogenesis of diabetic and cisplatin nephropathy was demonstrated in PAF receptor gene-targeted mouse, but, however, (4) significant co-relation between polymorphism of PAF acetylhydralase gene and pathogenesis and/or progression of diabetic nephropathy has not been shown so far.
These results will lead to new insight to the significances of lipid autacoids in the kidney.
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