title: Metformin alleviated EMT and fibrosis after renal ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  The purpose of this study is to assess the potential effects of metformin on the development of EMT and tubulointerstitial fibrosis 12 weeks after acute renal ischemia-reperfusion.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned to four groups: Sham, IRI, transient administration of metformin (TAM), and continuous administration of metformin (CAM). Metformin was administered i.p. at a dose of 125 μg kg (- 1) d( - 1) 3 d prior to suffering from IRI (TAM), or from 3 d before suffering from IRI to 12 weeks after reperfusion (CAM). Renal function, histology, and expressions of IL-6, TNF-α, α-SMA, TGF-β1, Vimentin, and E-cadherin were analyzed.
  
  
  RESULTS
  Tubulointerstitial fibrosis worsened further in IRI, accompanied by the increased expressions of interleukin-6, TNF-α, α-SMA, TGF-β1, Vimentin, and loss of E-cadherin. Although there were no significant differences between IRI and TAM (p > 0.05). Compared with the IRI, expressions of IL-6, TNF-α, α-SMA, TGF-β1, and Vimentin were reduced and the expression of E-cadherin was restored in CAM (p < 0.05). CAM also significantly promoted activation of AMPK (p < 0.05), which showed no difference among Sham, IRI, and TAM (p > 0.05).
  
  
  CONCLUSIONS
  CAM significantly attenuated tubulointerstitial fibrosis and EMT in rats, potentially via activation of AMPK and down-regulation of TGF-β1.
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Weng
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Jiang
authors.affiliation: a Department of Urology , Renmin Hospital of Wuhan University, Wuhan University , Wuhan , China.
authors.forename: Xiuheng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply* / Q000473:pathology*; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications
chemical_list: D008687:Metformin
keywords: Epithelial matrix transformation; fibrosis; ischemia–reperfusion injury; metformin; renal