Investigation for the role of collagen-binding integrin receptor in the development of renal fibrosis

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In order to prevent the progression of renal diseases, we investigated the role of collagen-binding integrin receptor in the development of renal fibrosis. Cell proliferation, migration and collagen contraction assays revealed that both alf3l integrin-mediated ERK/AP-1 and lintegrin-linked kinase (ILK)signalings are important pathways for pathological ECM remodeling seen in progressive glomerulonephritis (GN). Either function-blocking antibody, ERK inhibitor (PD98059) or dominant negative cDNA vector inhibited integrin-mediated signaling on in vitro ECM remodeling seen in progressive GN. Administration of integrin function-blocking anti-α1 integrin antibody into rats with anti-Thy-1 GN showed histological improvement with respect to MC proliferation and abnormal ECM remodeling compared with control anti-Thy-1 GN rats received control antibody. These results indicate that integrin-mediated signaling pathways play a critical role in pathological ECM remodeling in progressive renal fibrosis.