| Co-Investigator(Kenkyū-buntansha) |
SHIROTA Kinji Azabu University, Department of Veterinary Medicine, Professor, 獣医学部, 教授 (70147974)
OKADA Toshiya Osaka Prefecture University, College of Agriculture, Assistant Professor, 農学部, 助手 (00169111)
YAMATE Jyoji Osaka Prefecture University, College of Agriculture, Associate Professor, 農学部, 講師 (50150115)
OHASHO Fumihito Osaka Prefecture University, College of Agriculture, Professor, 農学部, 教授 (10126013)
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| Research Abstract |
In order to investigate the pathogenesis of renal fibrosis, first, we established animal models of rats ; acute and chronic cisplatin-induced renal fibrosis, renal fibrosis due to ureteral obstruction, and spontaneous chronic progressive nephropathy. In these models, it was demonstrated that infiltrated macrophages and myofibroblasts play important roles in development of renal fibrosis. In addition, it was found that apoptosis occures in the my ofibroplasts, resulting in a decrease in extracellular matrix and repairment of affected kidney. Furthermore, TGF-beta, a fibrogenic cytokine, may be produced by infiltrating macrophages in early stages of the fibrosis, whereas the production might be due to regenerating renal tubules in the late stages. Interestingly, PDGF, a fibrogenic cytokine, may contribute much greater to fibrosis than did TGF-beta in chronic progressive nephropathy ; the PDGF is secreted by regenerating renal tubular epithelial cells. To comparerenal fibrosis with fibrosis in other organs, we investigated the pathogenesis of hepatic fibrosis induced by CCI_4 and and myocardial fibrosis induced by isoproterenol ; in the hepatic and myocardial fibrosis models, it was also found that infiltrating macrophages and myofibroblasts (perisinusoidal cells in the liver) play central roles in the lesions. However, the contribution of macrophages was not demonstrated in the LEC rat hepatic fibrosis that are caused spontaneously by abnormal copper accumulation. In conclusion, these animal models established by us would become very useful tools for development of new chemicals effective for renal fibrosis, and the pathological findings obtaied should supply important information to the pathogenesis of renal fibrosis.
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