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

Abstract

This study was designed to investigate the putative protective effect of β-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 β-casomorphin-7-treatment group. All rats were euthanized after 30 days with or without β-casomorphin-7 treatment. Biochemical parameters including blood glucose and renal function were quantified. The concentration of plasma TGF-β1 was measured by ELISA. Histopathological changes to the kidney were studied by Masson and Sirius red staining. Expressions of α-smooth muscle actin (α-SMA), E-cadherin, vimentin, cytokeratin19 and TGF-β1 mRNA in rat renal cortices were analyzed by real-time PCR. Changes in α-SMA and E-cadherin protein expression in rat renal cortices were quantified by Western blot. β-Casomorphin-7 treatment of diabetic rats reduced urinary glucose, urinary protein, serum creatinine, blood urinary nitrogen, plasma TGF-β1 and the ratio of kidney: body weight. Masson and Sirius red staining showed that β-casomorphin-7 treatment attenuated renal interstitial fibrosis in diabetic rats. Compared to the control rats, diabetic rats had elevated expressions of α-SMA, vimentin and TGF-β1 mRNA and α -SMA protein and decreased expression of E-cadherin and cytokeratin19 mRNA, and E-cadherin protein. β-Casomorphin-7 treatment of diabetic rats partially normalized these changes. Our results suggest that administration of β-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.

• Authors: Wei Zhang, Jinfeng Miao, Chang Ma, Dongning Han, Yuanshu Zhang
• Journal: Peptides (Peptides) Vol. 36 Issue 2 Pg. 186-91 (Aug 2012) ISSN: 1873-5169 [Electronic] United States
• PMID: 22687367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Endorphins
• Peptide Fragments
• Transforming Growth Factor beta1
• beta-casomorphin 7

Topics

• Animals
• Blotting, Western
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Diabetic Nephropathies (drug therapy, metabolism)
• Endorphins (therapeutic use)
• Epithelial Cells (drug effects, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• Kidney Tubules (cytology)
• Male
• Peptide Fragments (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Transforming Growth Factor beta1 (genetics, metabolism)