Norcantharidin Inhibits Renal Interstitial Fibrosis by Blocking the Tubular Epithelial-Mesenchymal Transition

作者：Li, Ying^*; Sun, Yan; Liu, Fuyou; Sun, Lin; Li, Jun; Duan, Shaobin; Liu, Hong; Peng, Youming; Xiao, Li; Liu, Yuping; Xi, Yiyun; You, Yanhua; Li, Hua; Wang, Min; Wang, Shuai; Hou, Tao

来源：PLos One, 2013, 8(6): e66356.

DOI：10.1371/journal.pone.0066356

• TGF-BETA
• TUBULOINTERSTITIAL FIBROSIS
• OBSTRUCTIVE NEPHROPATHY
• DIABETIC-NEPHROPATHY
• URETERAL OBSTRUCTION
• SNAIL GENES
• EXPRESSION
• KIDNEY
• CELLS
• FIBROBLASTS

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 alpha-SMA and downregulation of E-cadherin in the rat kidney (P<0.05). Human renal proximal tubule cell lines (HK-2) stimulated with TGF-beta(1) were treated with different concentrations of NCTD. HK-2 cells stimulated by TGF-beta(1) in vitro led to downregulation of E-cadherin and increased de novo expression of alpha-SMA; co-treatment with NCTD attenuated all of these changes (P<0.05). NCTD reduced TGF-beta(1)-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.

• 出版日期2013-6-25
• 单位中南大学; 新疆医科大学