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BioMed Research International
Volume 2013, Article ID 308130, 12 pages
http://dx.doi.org/10.1155/2013/308130
Research Article

Dual Inhibiting Senescence and Epithelial-to-Mesenchymal Transition by Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction

1Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Khlong Nueng, Khlong Luang, Pathum Thani 12121, Thailand
2Division of Biochemistry, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University (Rangsit Campus), Khlong Nueng, Khlong Luang, Pathum Thani 12121, Thailand
3Department of Paediatric, Faculty of Medicine, Thammasat University (Rangsit Campus), Khlong Nueng, Khlong Luang, Pathum Thani 12121, Thailand

Received 17 July 2013; Revised 1 October 2013; Accepted 5 October 2013

Academic Editor: Youhua Liu

Copyright © 2013 Adis Tasanarong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-β1, BMP-7, Smad2/3, Smad1/5/8, and was determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-β1, Smad2/3, S100A4, and expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. was positively correlated with TGF-β1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-β, Smad2/3, S100A4, and and preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease.