Norcantharidin Inhibits Renal Interstitial Fibrosis by Blocking the Tubular Epithelial-Mesenchymal Transition |
| |
| Authors: | Ying Li Yan Sun Fuyou Liu Lin Sun Jun Li Shaobin Duan Hong Liu Youming Peng Li Xiao Yuping Liu Yiyun Xi Yanhua You Hua Li Min Wang Shuai Wang Tao Hou |
| |
| Affiliation: | 1. Division of Nephrology, Second Xiangya Hospital, Central South University, Changsha, P.R. China.; 2. Division of Nephrology, The first affiliated hospital, XinJiang Medical University,Uramuq, P.R. China.; 3. Department of Clinical Laboratory, Second Xiangya Hospital, Central South University, P.R. China.; University of Sao Paulo Medical School, Brazil, |
| |
| Abstract: | Epithelial–mesenchymal transition (EMT) is thought to contribute to the progression of renal tubulointerstitial fibrosis. Norcantharidin (NCTD) is a promising agent for inhibiting renal interstitial fibrosis. However, the molecular mechanisms of NCTD are unclear. In this study, a unilateral ureteral obstruction (UUO) rat model was established and treated with intraperitoneal NCTD (0.1 mg/kg/day). The UUO rats treated with NCTD showed a reduction in obstruction-induced upregulation of α-SMA and downregulation of E-cadherin in the rat kidney (P<0.05). Human renal proximal tubule cell lines (HK-2) stimulated with TGF-β1 were treated with different concentrations of NCTD. HK-2 cells stimulated by TGF-β1 in vitro led to downregulation of E-cadherin and increased de novo expression of α-SMA; co-treatment with NCTD attenuated all of these changes (P<0.05). NCTD reduced TGF-β1-induced expression and phosphorylation of Smad2/3 and downregulated the expression of Snail1 (P<0.05). These results suggest that NCTD antagonizes tubular EMT by inhibiting the Smad pathway. NCTD may play a critical role in preserving the normal epithelial phenotype and modulating tubular EMT. |
| |
| Keywords: | |
|
|
