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Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice.
J Med Assoc Thai. 2011 Dec; 94 Suppl 7:S1-9.JM

Abstract

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-beta) 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-beta 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-beta1. Protein expression of TGF-beta1 and Smad2/3 was determined by western blot analysis. The mRNA expression of TGF-beta1 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-beta1 protein expression in the interstitium area of obstructed kidneys. Moreover increasing of TGF-beta1 protein and upregulation of TGF-beta1 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-beta1 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-beta/Smad2/3 signaling pathway.

Authors+Show Affiliations

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

22619900

Citation

Tasanarong, Adis, et al. "Vitamin E Ameliorates Renal Fibrosis By Inhibition of TGF-beta/Smad2/3 Signaling Pathway in UUO Mice." Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, vol. 94 Suppl 7, 2011, pp. S1-9.
Tasanarong A, Kongkham S, Duangchana S, et al. Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice. J Med Assoc Thai. 2011;94 Suppl 7:S1-9.
Tasanarong, A., Kongkham, S., Duangchana, S., Thitiarchakul, S., & Eiam-Ong, S. (2011). Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice. Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, 94 Suppl 7, S1-9.
Tasanarong A, et al. Vitamin E Ameliorates Renal Fibrosis By Inhibition of TGF-beta/Smad2/3 Signaling Pathway in UUO Mice. J Med Assoc Thai. 2011;94 Suppl 7:S1-9. PubMed PMID: 22619900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice. AU - Tasanarong,Adis, AU - Kongkham,Supranee, AU - Duangchana,Soodkate, AU - Thitiarchakul,Supachai, AU - Eiam-Ong,Somchai, PY - 2012/5/25/entrez PY - 2012/5/25/pubmed PY - 2012/8/15/medline SP - S1 EP - 9 JF - Journal of the Medical Association of Thailand = Chotmaihet thangphaet JO - J Med Assoc Thai VL - 94 Suppl 7 N2 - 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-beta) 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-beta 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-beta1. Protein expression of TGF-beta1 and Smad2/3 was determined by western blot analysis. The mRNA expression of TGF-beta1 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-beta1 protein expression in the interstitium area of obstructed kidneys. Moreover increasing of TGF-beta1 protein and upregulation of TGF-beta1 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-beta1 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-beta/Smad2/3 signaling pathway. SN - 0125-2208 UR - https://www.unboundmedicine.com/medline/citation/22619900/Vitamin_E_ameliorates_renal_fibrosis_by_inhibition_of_TGF_beta/Smad2/3_signaling_pathway_in_UUO_mice_ L2 - https://medlineplus.gov/vitamine.html DB - PRIME DP - Unbound Medicine ER -