Xing Zhang1,2, Hong Lu3, Shuangshuang Xie2, Cunzao Wu4, Yangyang Guo1, Yanyi Xiao1, Shizhang Zheng1, Hengyue Zhu1, Yan Zhang4,5, Yongheng Bai1,5. 1. Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 2. Zhejiang University School of Medicine, Hangzhou, China. 3. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 4. Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 5. Institute of Kidney Health, Center for Health Assessment, Wenzhou Medical University, Wenzhou, China.
Abstract
BACKGROUND AND PURPOSE: Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. Previous studies have shown that resveratrol has anti-fibrotic activity, but its potential molecular mechanisms of action are not well understood. EXPERIMENTAL APPROACH: The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-β1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining. KEY RESULTS: Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast-myofibroblast differentiation (FMD) and epithelial-mesenchymal transition (EMT). The anti-fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation-related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/β-catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF-β1-induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation-related signalling. Similarly, TGF-β1-mediated overactivation of the proliferation-related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti-fibrotic and anti-proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype. CONCLUSIONS AND IMPLICATIONS: Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation-related pathways, making it a potential therapeutic agent for preventing renal fibrosis.
BACKGROUND AND PURPOSE:Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. Previous studies have shown that resveratrol has anti-fibrotic activity, but its potential molecular mechanisms of action are not well understood. EXPERIMENTAL APPROACH: The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-β1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining. KEY RESULTS:Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast-myofibroblast differentiation (FMD) and epithelial-mesenchymal transition (EMT). The anti-fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation-related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/β-catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF-β1-induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation-related signalling. Similarly, TGF-β1-mediated overactivation of the proliferation-related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti-fibrotic and anti-proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype. CONCLUSIONS AND IMPLICATIONS: Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation-related pathways, making it a potential therapeutic agent for preventing renal fibrosis.
Authors: Xiao-Ming Meng; Xiao Ru Huang; Jun Xiao; Hai-yong Chen; Xiang Zhong; Arthur C K Chung; Hui Yao Lan Journal: J Pathol Date: 2012-02-22 Impact factor: 7.996
Authors: Sin Young Choi; Zhe Hao Piao; Li Jin; Jung Ha Kim; Gwi Ran Kim; Yuhee Ryu; Ming Quan Lin; Hyung-Seok Kim; Hae Jin Kee; Myung Ho Jeong Journal: PLoS One Date: 2016-11-30 Impact factor: 3.240