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   Resveratrol inhibits renal interstitial fibrosis in diabetic nephropathy by regulating AMPK/NOX4/ROS pathway  
   
نویسنده He Ting ,Xiong Jiachuan ,Nie Ling ,Yu Yanlin ,Guan Xu ,Xu Xinli ,Xiao Tangli ,Yang Ke ,Liu Liang ,Zhang Daohai ,Huang Yunjian ,Zhang Jingbo ,Wang Junping ,Sharma Kumar ,Zhao Jinghong
منبع journal of molecular medicine - 2016 - دوره : 94 - شماره : 12 - صفحه:1359 -1371
چکیده    Renal interstitial fibrosis is a major pathologic feature of diabetic nephropathy, while the pathogenesis and therapeutic interventions of diabetic renal interstitial fibrosis are not well established. in this study, we first demonstrated that high glucose could induce renal fibroblast (nrk-49f) cell proliferation and activation to myofibroblasts, accompanied by a significant increase in the intracellular levels of reactive oxygen species (ros) derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (nox4). ros-mediated erk1/2 activation was found to play a crucial role in high glucose-induced fibroblast proliferation and activation. resveratrol, like the nox4-targeting small interfering rna (sirna), markedly inhibited high glucose-induced fibroblast proliferation and activation by reducing nox4-derived ros production. it was then revealed that the increase in the expression of nox4 induced by high glucose was due to the inactivation of amp-activated protein kinase (ampk), which could be reversed by resveratrol. further in vivo investigation demonstrated that resveratrol treatment significantly attenuated renal fibrosis in db/db mice, accompanied by an evident increase in phospho-ampk and decrease in nox4. in summary, our results suggest that high glucose can directly promote renal fibroblasts proliferation and activation in a ros-dependent manner, and resveratrol is a potential therapeutic agent against diabetic renal fibrosis via regulation of ampk/nox4/ros signaling.
کلیدواژه Resveratrol ,Diabetic nephropathy ,Reactive oxygen species ,NOX ,AMPK ,ERK 1/2
آدرس Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, Department of Nephrology, China, Third Military Medical University, State Key Laboratory of Trauma, China, University of California, Division of Nephrology-Hypertension, USA. Veterans Administration San Diego HealthCare System, USA, Third Military Medical University, Department of Nephrology, China
 
     
   
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