Upregulation ofα3β1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy

Abstract

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation ofα3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels ofα3β1-integrin in podocytes in early and advanced stages of DN.Methods. Surgical specimens from DN patients were examined byin situhybridization, and the expression levels ofα3- andβ1-integrin subunits in glomeruli of early (n=6) and advanced (n=8) stages were compared with those of normal glomeruli (n=5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined.Results. Podocytes of early-stage DN showed upregulation ofα3- andβ1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation ofα3- andβ1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhancedin vitromigration and attachment on collagen substrate.Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation ofα3β1-integrin.