Upregulation of alpha 3 beta 1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy

作者：Sawada Kaichiro; Toyoda Masao^*; Kaneyama Noriko; Shiraiwa Sawako; Moriya Hitomi; Miyatake Han; Tanaka Eitaro; Yamamoto Naoyuki; Miyauchi Masaaki; Kimura Moritsugu; Wada Takehiko; Fukagawa Masafumi

来源：Journal of Diabetes Research, 2016, 2016: 9265074.

DOI：10.1155/2016/9265074

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation of alpha 3 beta 1-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 of alpha 3 beta 1-integrin in podocytes in early and advanced stages of DN. Methods. Surgical specimens from DN patients were examined by in situ hybridization, and the expression levels of alpha 3-and beta 1-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-beta 1 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 of alpha 3-and beta 1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of alpha 3-and beta 1-integrin in HSMP cultured with TGF-beta 1. TGF-beta 1-stimulated HSMP also showed enhanced in vitro migration and attachment on collagen substrate. Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation of alpha 3 beta 1-integrin.

• 出版日期2016