title: Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition.
abstract: BACKGROUND
  Epithelial to mesenchymal transition (EMT) is a process which tubular epithelial cells (TEC) undergo a phenotypic conversion to the matrix-producing fibroblasts and myofibroblasts. Phenotypic alteration of TEC was induced by the important cytokine transforming growth factor-beta (TGF-beta) to development of renal fibrosis. However bone morphogenetic protein-7 (BMP-7) generally counteracts with TGF-beta to maintenance of epithelial phenotype. In the present study, the authors investigated the anti-fibrotic property of vitamin E on unilateral ureteral obstruction (UUO) model mice.
  
  
  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 operation. Kidney specimens were fixed for pathological study and immunohistochemistry for BMP-7. Protein expression of BMP-7 was determined by western blot analysis. The mRNA expression of BMP-7 and TGF-beta1 were measured by real-time RT-PCR.
  
  
  RESULTS
  Vitamin E treated UUO mice showed the less severity of renal fibrosis. Tubular atrophy and interstitial fibrosis were significantly attenuated in vitamin E treatment. Immunohistochemistry revealed decreasing of BMP-7 protein expression in cytoplasm of TEC in obstructed kidneys. Moreover decreasing of BMP-7 protein and downregulation of BMP-7 mRNA in UUO mice were confirmed by western blot and real time RT-PCR. In contrast, vitamin E treatment significantly maintained the expression of BMP-7 protein and mRNA in UUO mice compared with placebo treatment. On the other hand, TGF-beta1 mRNA expression showed progressive upregulation in UUO mice on day 3, 7 and 14 compared with sham controls. The expression of TGF-beta1 mRNA was significantly lower in all vitamin E treated UUO mice compared with placebo treatment.
  
  
  CONCLUSIONS
  Vitamin E treatment attenuated the progression of renal fibrosis in obstructed kidney by inhibited the TGF-beta1 but maintained the BMP-7 during EMT. Thus, the renoprotective effects of vitamin E could have some therapeutic value to inhibit the progression of renal fibrosis in human.
authors.affiliation: Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 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: Supachai
authors.initials: S
authors.lastname: Thitiarchakul
authors.forename: Somchai
authors.initials: S
authors.lastname: Eiam-Ong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D014517:Ureteral Obstruction / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D055419:Bone Morphogenetic Protein 7; D014810:Vitamin E