Vitamin e ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition
Tasanarong, A.; Kongkham, S.; Thitiarchakul, S.; Eiam-Ong, S.
Journal of the Medical Association of Thailand 94(Suppl 7): S10-S18
2011
ISSN/ISBN: 0125-2208 PMID: 22619901 Document Number: 16056
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. 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. 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. 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.