Original Report: Laboratory Investigation

Rapamycin Prevents Early Steps of the Development of Diabetic Nephropathy in Rats
Yi Yang, Jingjing Wang, Ling Qin, Zhangfei Shou, Jie Zhao, Huiping Wang, Ying Chen, Jianghua Chen

Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

Address of Corresponding Author

Am J Nephrol 2007;27:495-502 (DOI: 10.1159/000106782)

  Key Words

• Rapamycin
• Mammalian target of rapamycin
• Diabetic nephropathy

  Abstract

Background/Aims: Recent studies suggested the involvement of the Akt/mammalian target of rapamycin (mTOR) pathway in the pathogenesis of diabetic nephropathy. The effect of mTOR blockade by rapamycin in diabetic nephropathy was investigated, but in vivo study of rapamycin treatment in the course of early diabetes is still insufficient. This study was designed to determine the therapeutic effects of rapamycin on diabetic nephropathy at an early stage. Methods: Diabetes was induced in Sprague-Dawley rats with streptozotocin, and rapamycin (1 mg/kg) was administered by daily gavage for 4 weeks. Renal structural changes and some factors involved in the early pathogenesis of diabetic nephropathy were tested. The activation level of the Akt/mTOR pathway was also determined. Results: Rapamycin treatment reduced albuminuria, glomerular enlargement, glomerular basement membrane thickening, renal macrophage recruitment, and levels of renal mRNA expression of proliferating cell nuclear antigen, transforming growth factor-₁, vascular endothelial growth factor, and monocyte chemoattractant protein-1 without change in blood glucose level and blood pressure in experimental diabetic rats. In addition, treatment with rapamycin also down-regulated the enhanced levels of renal p-Akt, phospho-p70S6 kinase, and phospho-ribosomal S6 protein in diabetic rats. Conclusions: Rapamycin treatment can prevent the early renal structural changes of diabetes in experimental rats, and thus halt the early steps of the development of diabetic nephropathy. mTOR blockade might be beneficial for the treatment of diabetic nephropathy.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Jianghua Chen
Kidney Disease Center, the First Affiliated Hospital
College of Medicine, Zhejiang University
79 Qingchun Road, Hangzhou, 310003 (China)
Tel./Fax +86 571 8723 6992, E-Mail chenjianghua@zju.edu.cn

  Article Information

Received: May 16, 2007
Accepted: June 20, 2007
Published online: July 31, 2007
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 3, Number of References : 31