J Med Assoc Thai 2011; 94 (12):1

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Vitamin E Ameliorates Renal Fibrosis by Inhibition of TGF-β/Smad2/3 Signaling Pathway in UUO Mice
Tasanarong A Mail, Kongkham S , Duangchana S , Thitiarchakul S , Eiam-Ong S

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-β) 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-β 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-β1. Protein expression of TGF-β1 and Smad2/3 was determined by western blot analysis. The mRNA expression of TGF-β1 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-β1 protein expression in the interstitium area of obstructed kidneys. Moreover, increasing of TGF-β1 protein and upregulation of TGF-β1 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-β1 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-β/Smad2/3 signaling pathway.

Keywords: Vitamin E, TGF-β1, Smad2/3, Renal fibrosis


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