title: 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.affiliation: Division of Nephrology, Second Xiangya Hospital, Central South University, Changsha, PR China. mail: yachi20101213@gmail.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Shaobin
authors.initials: S
authors.lastname: Duan
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Youming
authors.initials: Y
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Xi
authors.forename: Yanhua
authors.initials: Y
authors.lastname: You
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Hou
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015820:Cadherins; D051899:Smad2 Protein; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat; C498862:Acta2 protein, rat; C069741:norcantharidin