title: Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice.
abstract: BACKGROUND
  One striking feature of chronic kidney disease (CKD) is tubular atrophy and interstitial fibrosis (TA/IF). During chronic renal injury, transforming growth factor-beta (TGF-beta) is involved in this process causing progression of renal fibrosis. Smad2/3 proteins have been identified to have an important function in the expression of extracellular matrix (ECM) regulation through TGF-beta signaling pathway. In the present study, the authors investigated the effect of vitamin E on renal fibrosis in mice model of unilateral ureteral obstruction (UUO).
  
  
  METHODS
  UUO or sham-operated mice were randomly assigned to receive vitamin E (alpha tocopherol) or placebo and were sacrificed on days 3, 7 and 14 after UUO or sham operation. Kidney specimens were fixed for pathological study and immunohistochemistry for TGF-beta1. Protein expression of TGF-beta1 and Smad2/3 was determined by western blot analysis. The mRNA expression of TGF-beta1 was measured by real-time RT-PCR.
  
  
  RESULTS
  Vitamin E treated UUO mice had less severity of renal fibrosis than placebo treatment. TA/IF was significantly attenuated by vitamin E treatment. Immunohistochemistry revealed increasing of TGF-beta1 protein expression in the interstitium area of obstructed kidneys. Moreover increasing of TGF-beta1 protein and upregulation of TGF-beta1 mRNA in UUO mice were confirmed by western blot and real time RT-PCR. In contrast, vitamin E treatment significantly inhibited the expression of TGF-beta1 protein and mRNA in UUO mice compared with placebo treatment. Interestingly, Smad2/3 protein expression became progressive increasing in UUO mice on day 3, 7 and 14 compared with sham controls. The expression of Smad2/3 protein was significantly lower in vitamin E treated UUO mice than placebo treatment in any time points.
  
  
  CONCLUSIONS
  Vitamin E treatment attenuated the progression of renal fibrosis in obstructed kidneys. The renoprotective effect of vitamin E could be mediated by inhibition of TGF-beta/Smad2/3 signaling pathway.
authors.affiliation: Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumtani, Thailand. adis_tasanarong@hotmail.com
authors.forename: Adis
authors.initials: A
authors.lastname: Tasanarong
authors.forename: Supranee
authors.initials: S
authors.lastname: Kongkham
authors.forename: Soodkate
authors.initials: S
authors.lastname: Duangchana
authors.forename: Supachai
authors.initials: S
authors.lastname: Thitiarchakul
authors.forename: Somchai
authors.initials: S
authors.lastname: Eiam-Ong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta; D014810:Vitamin E