Journal
AMERICAN JOURNAL OF NEPHROLOGY
Volume 31, Issue 4, Pages 363-374Publisher
KARGER
DOI: 10.1159/000300388
Keywords
Resveratrol; Diabetic nephropathy; Adenosine monophosphate-activated protein kinase; Renal mesangial cells; Hypertrophy; Eukaryotic translation initiation factor 4E binding protein 1; Phospho-ribosomal protein S6
Categories
Funding
- Medical Science and Technology Development Foundation, Nanjing Department of Health [YKK08136]
- National Natural Science Foundation of Jiangsu Department of Education [07KJD320141]
Ask authors/readers for more resources
Background: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms. Method: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of earlystage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring H-3-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phosphoribosomal protein S6 (S6) was analyzed by Western blot. Results: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. Conclusion: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN. Copyright (C) 2010 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available