Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2013, Article ID 463740, 8 pages
http://dx.doi.org/10.1155/2013/463740
Research Article

Both ERK/MAPK and TGF-Beta/Smad Signaling Pathways Play a Role in the Kidney Fibrosis of Diabetic Mice Accelerated by Blood Glucose Fluctuation

1Department of Endocrinology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
2Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China

Received 9 October 2012; Revised 18 April 2013; Accepted 15 May 2013

Academic Editor: Shahidul Islam

Copyright © 2013 Xiaoyun Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF) under high glucose condition on kidney in the mice. Methods. The diabetic and BGF animal models were established in this study. Immunohistochemistry, Western blot, and RT-PCR analysis were applied to detect the expression of type I collagen, matrix metalloproteinase-1 (MMP1), metalloproteinase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGF-β1), phosphorylated-ERK, p38, smad2/3, and Akt. Results. BGF treatment increased type I collagen synthesis by two times compared with the control. The expression of MMP1 was reduced markedly while TIMP1 synthesis was enhanced after BGF treatment. ERK phosphorylation exhibits a significant increase in the mice treated with BGF. Furthermore, BGF can markedly upregulate TGF-β1 expression. The p-smad2 showed 2-fold increases compared with the only diabetic mice. However, p-AKT levels were unchanged after BGF treatment. Conclusions. These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF-β/smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation.