Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice

J Med Assoc Thai. 2011 Dec;94 Suppl 7:S1-9.

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).

Material and method: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Fibrosis / etiology
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Kidney / metabolism
  • Kidney / pathology*
  • Male
  • Mice
  • Signal Transduction
  • Smad Proteins, Receptor-Regulated / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / metabolism
  • Ureteral Obstruction / pathology*
  • Vitamin E / pharmacology
  • Vitamin E / therapeutic use*

Substances

  • Antioxidants
  • Smad Proteins, Receptor-Regulated
  • Transforming Growth Factor beta
  • Vitamin E