Norcantharidin inhibits renal interstitial fibrosis by blocking the tubular epithelial-mesenchymal transition.

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.

• 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
• Journal: PloS one (PLoS One) Vol. 8 Issue 6 Pg. e66356 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23825538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Bridged Bicyclo Compounds, Heterocyclic
• Cadherins
• SNAI1 protein, human
• Smad2 Protein
• Smad3 Protein
• Snai2 protein, rat
• Snail Family Transcription Factors
• Transcription Factors
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• norcantharidin

Topics

• Actins (genetics)
• Animals
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cadherins (genetics)
• Cell Line
• Epithelial-Mesenchymal Transition (drug effects)
• Fibrosis
• Gene Expression Regulation (drug effects)
• Humans
• Kidney Tubules (drug effects, metabolism, pathology)
• Male
• Phenotype
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Smad2 Protein (genetics, metabolism)
• Smad3 Protein (genetics, metabolism)
• Snail Family Transcription Factors
• Transcription Factors (genetics)
• Transforming Growth Factor beta1 (metabolism, pharmacology)
• Ureteral Obstruction (genetics, metabolism, pathology)