title: Resveratrol attenuates renal injury and fibrosis by inhibiting transforming growth factor-β pathway on matrix metalloproteinase 7.
abstract: Renal injury has a strong relationship to the subsequent development of renal fibrosis. In developing renal fibrosis, tubular epithelial cells in the kidney underwent epithelial-mesenchymal transition (EMT). Matrix metalloproteinase 7 (MMP7) was reported to reduce E-cadherin and induce EMT by up-regulation of β-catenin/lymphoid enhancer-binding factor 1 (LEF1) signaling. In this research, we tried to evaluate the role of resveratrol (RSV) on EMT process in renal injury and fibrosis. Human tubular epithelial cell HK-2 cells were treated with aristolochic acid (AAs) and transforming growth factor-β(TGF-β) to induce EMT with or without the administration of RSV. The inhibitory role of RSV on EMT in renal injury and fibrosis was determined by Western blotting, real-time PCR, and immunofluorescence staining. The EMT repressing role of RSV was also evaluated in vivo by renal ischemia-reperfusion (I/R) injury and unilateral ureteral obstruction (UUO) models. The underlying mechanism was investigated by shRNA interfering MMP7 and sirtuin 1 (SIRT1) expression. The results indicated that RSV reversed human kidney 2 (HK-2) cell EMT, renal I/R injury, and renal fibrosis. MMP7 inhibition was responsible for RSV-induced EMT repression. SIRT1 was up-regulated by RSV inhibited TGF-β pathway on MMP7 via deacetylating Smad4. In conclusion, RSV attenuated renal injury and fibrosis by inhibiting EMT process which was attributed to the fact that the up-regulated SIRT1 by RSV deacetylated Smad4 and inhibited MMP7 expression.
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Zhou
authors: Z
authors: Xiao
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Chen
authors: C
authors: Chen
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Ting
authors: T
authors: Meng
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha 410008, China Renal Diseases and Hypertension, Department of Internal Medicine, University of Texas Medical School at Houston, Houston 77030, TX, USA.
authors: Wenzheng
authors: W
authors: Zhang
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha 410008, China zhouqiaoll@yeah.net.
authors: Qiaoling
authors: Q
authors: Zhou
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis / Q000517:prevention & control*; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D013267:Stilbenes; D016212:Transforming Growth Factor beta; D020783:Matrix Metalloproteinase 7; D000077185:Resveratrol
keywords: Resveratrol; epithelial–mesenchymal; matrix metalloproteinase 7; renal fibrosis; transition