Vitamin E Ameliorates Renal Fibrosis in Ureteral Obstruction:Role of Maintaining BMP-7 during Epithelial-to-Mesenchymal Transition
Adis Tasanarong MD*,***, Supranee Kongkham PhD**, Supachai Thitiarchakul MD*, Somchai Eiam-Ong MD****
Affiliation : * Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, Thailand ** Division of Biochemistry, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 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 : 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-β (TGF-β) to development of renal fibrosis. However, bone morphogenetic
protein-7 (BMP-7) generally counteracts with TGF-β 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.
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 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-β1 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-β1
mRNA expression showed progressive upregulation in UUO mice on day 3, 7 and 14 compared with sham controls. The
expression of TGF-β1 mRNA was significantly lower in all vitamin E treated UUO mice compared with placebo treatment.
Conclusion : Vitamin E treatment attenuated the progression of renal fibrosis in obstructed kidney by inhibited the TGF-β1
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.
Keywords : Renal fibrosis, Vitamin E, BMP-7, TGF-β1, EMT
