Resveratrol prevents high glucose-induced epithelial–mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway

• Published in: Molecular and cellular endocrinology 2015-02, Vol.402, p.13-20
• Main Authors: He, Ting, Guan, Xu, Wang, Song, Xiao, Tangli, Yang, Ke, Xu, Xinli, Wang, Junping, Zhao, Jinghong
• Format: Article
• Language: English
• Subjects: Activation; Antioxidants - pharmacology; Blocking; Cell Line; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Drug Evaluation, Preclinical; Epithelial Cells - physiology; Epithelial-Mesenchymal Transition - drug effects; Epithelial–mesenchymal transition; Extracellular signal-regulated kinase 1/2; Glucose; Glucose - physiology; Humans; Inhibitors; Kidney; Kidney Tubules - pathology; Kinases; MAP Kinase Signaling System; NADPH Oxidase 1; NADPH Oxidase 4; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Nicotinamide adenine dinucleotide; Oxidase; Pathways; Reactive oxygen species; Reactive Oxygen Species - metabolism; Resveratrol; Stilbenes - pharmacology
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2014.12.010

•Resveratrol inhibits high glucose-induced EMT in HK-2 cells by decreasing intracellular ROS generation.•Resveratrol inhibits high glucose-induced ROS production in HK-2 cells via down-regulation of NOX1 and NOX4.•ROS-activated ERK1/2 signaling is involved in high glucose-induced EMT in HK-2 cells.•Resveratrol inhibits high glucose-induced EMT in HK-2 cells through the suppression of NADPH oxidase/ROS/ERK1/2 pathway. Resveratrol (RSV) is reported to have renoprotective activity against diabetic nephropathy, while the mechanisms underlying its function have not been fully elucidated. In this study, we investigate the effect and related mechanism of RSV against high glucose-induced epithelial to mesenchymal transition (EMT) in human tubular epithelial cells (HK-2). A typical EMT is induced by high glucose in HK-2 cells, accompanied by increased levels of reactive oxygen species (ROS). RSV exhibits a strong ability to inhibit high glucose-induced EMT by decreasing intracellular ROS levels via down-regulation of NADPH oxidase subunits NOX1 and NOX4. The activation of extracellular signal-regulated kinase (ERK1/2) is found to be involved in high glucose-induced EMT in HK-2 cells. RSV, like NADPH oxidase inhibitor diphenyleneiodonium, can block ERK1/2 activation induced by high glucose. Our results demonstrate that RSV is a potent agent against high glucose-induced EMT in renal tubular cells via inhibition of NADPH oxidase/ROS/ERK1/2 pathway.