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Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition.
J Med Assoc Thai. 2011 Dec; 94 Suppl 7:S10-8.JM

Abstract

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-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.

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-beta1 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-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.

CONCLUSION

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.

Authors+Show Affiliations

Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, Thailand. adis_tasanarong@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22619901

Citation

Tasanarong, Adis, et al. "Vitamin E Ameliorates Renal Fibrosis in Ureteral Obstruction: Role of Maintaining BMP-7 During Epithelial-to-mesenchymal Transition." Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, vol. 94 Suppl 7, 2011, pp. S10-8.
Tasanarong A, Kongkham S, Thitiarchakul S, et al. Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition. J Med Assoc Thai. 2011;94 Suppl 7:S10-8.
Tasanarong, A., Kongkham, S., Thitiarchakul, S., & Eiam-Ong, S. (2011). Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition. Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, 94 Suppl 7, S10-8.
Tasanarong A, et al. Vitamin E Ameliorates Renal Fibrosis in Ureteral Obstruction: Role of Maintaining BMP-7 During Epithelial-to-mesenchymal Transition. J Med Assoc Thai. 2011;94 Suppl 7:S10-8. PubMed PMID: 22619901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin E ameliorates renal fibrosis in ureteral obstruction: role of maintaining BMP-7 during epithelial-to-mesenchymal transition. AU - Tasanarong,Adis, AU - Kongkham,Supranee, AU - Thitiarchakul,Supachai, AU - Eiam-Ong,Somchai, PY - 2012/5/25/entrez PY - 2012/5/25/pubmed PY - 2012/8/15/medline SP - S10 EP - 8 JF - Journal of the Medical Association of Thailand = Chotmaihet thangphaet JO - J Med Assoc Thai VL - 94 Suppl 7 N2 - 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-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. 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-beta1 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-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. CONCLUSION: 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. SN - 0125-2208 UR - https://www.unboundmedicine.com/medline/citation/22619901/Vitamin_E_ameliorates_renal_fibrosis_in_ureteral_obstruction:_role_of_maintaining_BMP_7_during_epithelial_to_mesenchymal_transition_ L2 - https://medlineplus.gov/vitamine.html DB - PRIME DP - Unbound Medicine ER -