Abstract

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. An important histological hallmark of DN is proliferation of mesangial cells, and as a result, the expansion of extracellular matrix in the mesangium. Resveratrol has been shown to ameliorate hyperglycemia in diabetic rats. However, the effects of resveratrol on DN remain unknown. The aim of the present study is to investigate the effects of resveratrol on mesangial cell proliferation induced by advanced glycation end products (AGEs). Cultured rat mesangial cells were exposed to AGEs in the absence and presence of indicated concentrations of resveratrol (2.5, 5.0 and 10.0 µmol/L). The proliferation of mesangial cells was assayed by Methylthiazoletetrazolium (MTT) assay. Cell cycle and apoptosis were analyzed using flow cytometry. Expressions of glutathione S-transferases Mu (GSTM) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were detected by Western blot. Resveratrol inhibited proliferation of mesangial cells caused by AGEs, and down-regulated GSTM and Nrf2 expressions in a dose-dependent manner. S phase cell number significantly increased in the resveratrol treated groups compared with those in the AGEs group. Resveratrol inhibited mesangial cell proliferation induced by AGEs. The inhibitory effects of resveratrol were mediated in part through suppressing cell growth by arresting cells at the S phase of the cell cycle and down-regulating GSTM and Nrf2 expression. These findings suggested that resveratrol had potential preventive effects on the process of DN.

Key words: Resveratrol, diabetic nephropathy, mesangial cell, cell cycle, glutathione S-transferases Mu (GSTM), nuclear factor-erythroid 2-related factor 2 (Nrf2).