title: The T-box transcription factor Brachyury promotes renal interstitial fibrosis by repressing E-cadherin expression.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) induced by TGF-β1 is one of well-recognized factors contributing to renal fibrosis. However, the underlying molecular mechanisms of EMT are not fully understood. Brachyury, an evolutionarily conserved transcription factor, was recently identified as an important factor promoting EMT in human carcinoma cell lines. There is no evidence that Brachyury is involved in renal tubular EMT.
  
  
  RESULTS
  Our results demonstrated that Brachyury was prominently induced in TGF-β1-treated human proximal tubular epithelial (HK-2) cells and that this induction was accompanied by changes characteristic of EMT. Blockage of Brachyury expression by short interfering RNA (siRNA) in HK-2 cells effectively reversed the TGF-β1-induced EMT phenotype. Brachyury induction repressed E-cadherin transcription; the E-cadherin promoter contains a Brachyury binding site, and decreased expression of E-cadherin occurred in Brachyury-overexpressing cells when they were transfected with reporter constructs using the promoter. This effect was partially mediated by Slug and Snail, as knockdown of Snail and Slug by siRNA effectively reversed Brachyury-mediated EMT and partially restored E-cadherin expression. The expression of Brachyury also presented in a rat model of obstructive nephropathy and in tubulointerstitial fibrosis tissues of IgA nephropathy, suggesting that it may have a role in EMT and renal fibrosis in vivo.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that Brachyury plays an important role in regulating TGF-β1-mediated renal EMT and could be an attractive target for progression of renal disease therapies.
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. sunshiren@medmail.com.cn.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi, China. sunshiren@medmail.com.cn.
authors.forename: Shiren
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. sunec2010@163.com.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi, China. sunec2010@163.com.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi, China. xialin@fmmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. minmin_0905@163.com.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi, China. minmin_0905@163.com.
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. durui1979@aliyun.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Du
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. 43218204@qq.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. lr5276@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. whm@medmail.com.cn.
authors.forename: Hanmin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, 169 Chang le West Road, Xi'an, Shaanxi Province, 710032, China. huangchen@fmmu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017207:Rats, Sprague-Dawley; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D015820:Cadherins; D005326:Fetal Proteins; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000098908:Brachyury Protein; C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat