title: Resveratrol attenuates diabetic nephropathy via modulating angiogenesis.
abstract: Angiogenesis plays an important role in the pathogenesis of diabetic nephropathy (DN). In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with antiangiogenic activity in DN. In a type 1 diabetic rat model, resveratrol treatment blunted the increases of urine albumin excretion, kidney weight and creatinine clearance rate. The increases of glomerular diameter, mesangium accumulation, glomerular basement membrane thickness and renal fibrosis in diabetic rats were also reduced by resveratrol treatment. In the diabetic kidney, increased expression of vascular endothelial growth factor (VEGF), Flk-1 and angiopoietin 2, and reduced expression of Tie-2 were observed. These changes in angiogenic hormones and associated receptors were attenuated by resveratrol treatment. No changes in angiopoietin 1 expression were detected among each group of rats. Resveratrol also significantly downregulated high glucose-induced VEGF and Flk-1 expressions in cultured mouse glomerular podocytes and endothelial cells, respectively. These effects were attenuated by knocking-down silent information regulator 1 (Sirt1) expression. In contrast, upregulation of Sirt1 in cultured endothelial cells reduced Flk-1 expression. Increased permeability and cellular junction disruption of cultured endothelial cells caused by VEGF were also inhibited by resveratrol pretreatment. Taken together, the present study demonstrated that resveratrol may attenuate DN via modulating angiogenesis.
authors: Department of Internal Medicine, Huashan Hospital, Fudan University, Shanghai, China.
authors: Donghai
authors: D
authors: Wen
authors: Xinzhong
authors: X
authors: Huang
authors: Min
authors: M
authors: Zhang
authors: Liying
authors: L
authors: Zhang
authors: Jing
authors: J
authors: Chen
authors: Yong
authors: Y
authors: Gu
authors: Chuan-Ming
authors: CM
authors: Hao
mesh_terms: D043924:Angiogenesis Modulating Agents / Q000627:therapeutic use*; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043924:Angiogenesis Modulating Agents; D042702:Angiopoietin-2; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol