title: Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway.
abstract: 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.
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury of PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Tangli
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury of PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: zhaojh@tmmu.edu.cn.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005947:Glucose / Q000502:physiology; D006801:Humans; D007668:Kidney; D007684:Kidney Tubules / Q000473:pathology; D020935:MAP Kinase Signaling System; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C498910:NOX4 protein, human; D005947:Glucose; D000077185:Resveratrol
keywords: Diabetic nephropathy; Epithelial–mesenchymal transition; Extracellular signal-regulated kinase 1/2; Reactive oxygen species; Resveratrol