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

被引：25

作者：

Li, Ying ^{[1
]}

Sun, Yan ^{[2
]}

Liu, Fuyou ^{[1
]}

Sun, Lin ^{[1
]}

Li, Jun ^{[1
]}

Duan, Shaobin ^{[1
]}

Liu, Hong ^{[1
]}

Peng, Youming ^{[1
]}

Xiao, Li ^{[1
]}

Liu, Yuping ^{[1
]}

Xi, Yiyun ^{[1
]}

You, Yanhua ^{[1
]}

Li, Hua ^{[1
]}

Wang, Min ^{[3
]}

Wang, Shuai ^{[1
]}

Hou, Tao ^{[1
]}

机构：

[1] Cent S Univ, Xiangya Hosp 2, Div Nephrol, Changsha, Hunan, Peoples R China

[2] XinJiang Med Univ, Affiliated Hosp 1, Div Nephrol, Uramuq, Peoples R China

[3] Cent S Univ, Xiangya Hosp 2, Dept Clin Lab, Changsha, Hunan, Peoples R China

来源：

PLOS ONE | 2013年 / 8卷 / 06期

基金：

中国国家自然科学基金;

关键词：

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

D O I：

10.1371/journal.pone.0066356

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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