Effects of Troglitazone on the Expression of VEGF and TGF-β in Cultured Rat Mesangial Cells

Abstract

Background: Clinical study reported that troglitazone ameliorated microalbuminuria in diabetic nephropathy. However, the mechanism of action is not fully understood. Vascular endothelial growth factor (VEGF) is known as vascular permeability factor and it is considered the most likely cause of glomerular hyperfiltration and proteinuria in diabetic nephropathy. Transforming growth factor-beta (TGF-β) is a potent inducer of extracellular matrix production and fibrosis in renal cells and one of the important cytokine in the pathogenesis of diabetic nephropathy. To determine whether troglitazone affects VEGF and TGF-β production in diabetic nephropathy, we examined the effects of troglitazone on the VEGF and TGF-β expression in cultured rat mesangial cells exposed to high glucose concentration.Methods: Rat mesangial cells were cultured in media with D-glucose 5.5 mM (NG) or D-glucose 30 mM (HG), or D-glucose 30 mM/troglitazone 20 μM (HTz) and for 6, 24, or 72 hours, respectively. VEGF and TGF-β expression were assessed by semiquantitative RT-PCR and western blot analysis.Results: Troglitazone decreased the VEGF164 and VEGF120 mRNA expressions in cultured rat mesangial cells exposed to high glucose concentration with incubation for 24 and 72 hours, respectively. VEGF protein was also decreased in experimental group treated with troglitazone (HTz) than in those with HG for 24 and 72 hours. However troglitazone had no effect on the expression of TGF-β mRNA in mesangial cells. Conclusion: This study suggested that troglitazone may modulate the development and progression of diabetic nephropathy by reducing the expression of VEGF in mesangial cells (J Kor Diabetes Assoc 31:220~229, 2007)