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- Day 4, May 18（Fri.） Poster
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4P-12 PDF
Elucidation of renal fibrogenesis in Goto-Kakizaki rats by a proteomic study
Goto-Kakizaki (GK) rat is a spontaneous animal model of type 2 diabetes and early stage of diabetic nephropathy, which was developed by the selective breeding of glucose-intolerant Wistar rats. Herein, we performed 2-dimensional fluorescence difference gel electrophoresis between kidney of GK and Wistar rats, and clarified the change of protein profile of GK kidney. We identified 87 proteins as the differentially expressed proteins in GK kidney. Based on gene ontology analyses, we focused on the reduction of fumarate hydratase (FH) and the elevation of 2-oxoglutarate dehydrogenase (OGDH) in proteomic changes of GK kidney, and indicated that fumarate, which was involved in renal fibrogenesis, was increased in GK kidney compared with Wistar. We assessed renal fibrogenesis in GK rats by Azan staining, demonstrating that fibrogenesis was not induced at 15 weeks, but done at 33 weeks. Furthermore, both TGF-β and HIF-α, which were reported to induce renal fibrogenesis in diabetic nephropathy, were enhanced in GK kidney at 15 weeks. These results indicate that the reduction of FH and the elevation of OGDH may cause the accumulation of fumarate, the enhancement of TGF-β and HIF-α, and the induction of fibrogenesis in GK kidney.