Vitamin E Ameliorates Renal Fibrosis by Inhibition of TGF-βββββ/Smad2/3 Signaling Pathway in UUO Mice
Adis Tasanarong MD*,*** Supranee Kongkham PhD**, Soodkate Duangchana MD*, Supachai Thitiarchakul MD*, Somchai Eiam-Ong MD****
Affiliation : * Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumtani, Thailand ** Division of Biochemistry, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumtani, Thailand *** Inter-Department of Biomedical Sciences, Graduate School, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. **** Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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 intersti-
tium 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
