Investigation of Integrin-mediated MAP kinase Signaling in Glomerulonephritis

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In order to control the function and behaviors of glomerular mesangial cell(MC) in progressive glomerulonephritis(GN), we investigated the integrin-mediated cell signaling pathway involved in MC adhesion on extracellular matrix (ECM). Cell proliferation, migration and collagen contraction assays revealed that α1β1 integrin -mediated ERK/AP-1 signaling is important pathway for pathological ECM remodeling seen in progressive GN. Either function-blocking antibody, ERK inhibitor (PD98059) or dominant negative c-jun vector (TAM67) inhibited α1β1 integrin -mediated ERK/AP-1 signaling in MC-induced pathological ECM remodeling. Administration of 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 MC- α1β1 integrin- mediated ERK/AP-1 signaling play a critical role in pathological ECM remodeling in progressive GN.