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Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction.
Biomed Res Int. 2013; 2013:308130.BR

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 p16(INK4a) 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 p16(INK4a) expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. p16(INK4a) 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 p16(INK4a) 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.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

24350257

Citation

Tasanarong, Adis, et al. "Dual Inhibiting Senescence and Epithelial-to-mesenchymal Transition By Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction." BioMed Research International, vol. 2013, 2013, p. 308130.
Tasanarong A, Kongkham S, Khositseth S. Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction. Biomed Res Int. 2013;2013:308130.
Tasanarong, A., Kongkham, S., & Khositseth, S. (2013). Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction. BioMed Research International, 2013, 308130. https://doi.org/10.1155/2013/308130
Tasanarong A, Kongkham S, Khositseth S. Dual Inhibiting Senescence and Epithelial-to-mesenchymal Transition By Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction. Biomed Res Int. 2013;2013:308130. PubMed PMID: 24350257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual inhibiting senescence and epithelial-to-mesenchymal transition by erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal fibrosis in unilateral ureteral obstruction. AU - Tasanarong,Adis, AU - Kongkham,Supranee, AU - Khositseth,Sookkasem, Y1 - 2013/11/19/ PY - 2013/07/17/received PY - 2013/10/01/revised PY - 2013/10/05/accepted PY - 2013/12/19/entrez PY - 2013/12/19/pubmed PY - 2014/8/12/medline SP - 308130 EP - 308130 JF - BioMed research international JO - Biomed Res Int VL - 2013 N2 - 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 p16(INK4a) 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 p16(INK4a) expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. p16(INK4a) 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 p16(INK4a) 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. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/24350257/Dual_inhibiting_senescence_and_epithelial_to_mesenchymal_transition_by_erythropoietin_preserve_tubular_epithelial_cell_regeneration_and_ameliorate_renal_fibrosis_in_unilateral_ureteral_obstruction_ L2 - https://doi.org/10.1155/2013/308130 DB - PRIME DP - Unbound Medicine ER -