β-Casomorphin-7 attenuates the development of nephropathy in type I diabetes via inhibition of epithelial-mesenchymal transition of renal tubular epithelial cells

This study was designed to investigate the putative protective effect of beta-casomorphin-7 on diabetic nephropathy in a rat model, and to explore the possible mechanism of this effect. SD rats were randomly divided into the following three groups: control group, diabetes group and beta-casomorphin-7-treatment group. All rats were euthanized after 30 days with or without beta-casomorphin-7 treatment. Biochemical parameters including blood glucose and renal function were quantified. The concentration of plasma TGF-beta 1 was measured by ELISA. Histopathological changes to the kidney were studied by Masson and Sirius red staining. Expressions of alpha-smooth muscle actin (alpha-SMA), E-cadherin, vimentin, cytokeratin19 and TGF-beta 1 mRNA in rat renal cortices were analyzed by real-time PCR. Changes in alpha-SMA and E-cadherin protein expression in rat renal cortices were quantified by Western blot. beta-Casomorphin-7 treatment of diabetic rats reduced urinary glucose, urinary protein, serum creatinine, blood urinary nitrogen, plasma TGF-beta 1 and the ratio of kidney: body weight. Masson and Sirius red staining showed that beta-casomorphin-7 treatment attenuated renal interstitial fibrosis in diabetic rats. Compared to the control rats, diabetic rats had elevated expressions of alpha-SMA, vimentin and TGF-beta 1 mRNA and alpha-SMA protein and decreased expression of E-cadherin and cytokeratin19 mRNA, and E-cadherin protein. beta-Casomorphin-7 treatment of diabetic rats partially normalized these changes. Our results suggest that administration of beta-casomorphin-7 attenuates renal interstitial fibrosis caused by diabetes. This protective effect may be associated, in part, with down regulation of epithelial-mesenchymal transition of renal tubular epithelial cells. (C) 2012 Elsevier Inc. All rights reserved.