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Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition.
J Am Soc Nephrol. 2007 May; 18(5):1497-507.JA

Abstract

The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.

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Authors+Show Affiliations

Park SH
Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
Choi MJ
No affiliation info available
Song IK
No affiliation info available
Choi SY
No affiliation info available
Nam JO
No affiliation info available
Kim CD
No affiliation info available
Lee BH
No affiliation info available
Park RW
No affiliation info available
Park KM
No affiliation info available
Kim YJ
No affiliation info available
Kim IS
No affiliation info available
Kwon TH
No affiliation info available
Kim YL
No affiliation info available

MeSH

ActinsAnimalsCells, CulturedDisease ProgressionDogsEpithelial CellsErythropoietinFibronectinsFibrosisHumansKidneyKidney DiseasesMaleMesodermMiceMice, Inbred BALB CRecombinant ProteinsTransforming Growth Factor beta1Ureteral Obstruction

Pub Type(s)

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

Language

eng

PubMed ID

17389738

Citation

Park, Sun-Hee, et al. "Erythropoietin Decreases Renal Fibrosis in Mice With Ureteral Obstruction: Role of Inhibiting TGF-beta-induced Epithelial-to-mesenchymal Transition." Journal of the American Society of Nephrology : JASN, vol. 18, no. 5, 2007, pp. 1497-507.
Park SH, Choi MJ, Song IK, et al. Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition. J Am Soc Nephrol. 2007;18(5):1497-507.
Park, S. H., Choi, M. J., Song, I. K., Choi, S. Y., Nam, J. O., Kim, C. D., Lee, B. H., Park, R. W., Park, K. M., Kim, Y. J., Kim, I. S., Kwon, T. H., & Kim, Y. L. (2007). Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition. Journal of the American Society of Nephrology : JASN, 18(5), 1497-507.
Park SH, et al. Erythropoietin Decreases Renal Fibrosis in Mice With Ureteral Obstruction: Role of Inhibiting TGF-beta-induced Epithelial-to-mesenchymal Transition. J Am Soc Nephrol. 2007;18(5):1497-507. PubMed PMID: 17389738.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition. AU - Park,Sun-Hee, AU - Choi,Min-Jeong, AU - Song,In-Kyung, AU - Choi,Soon-Youn, AU - Nam,Ju-Ock, AU - Kim,Chan-Duck, AU - Lee,Byung-Heon, AU - Park,Rang-Woon, AU - Park,Kwon Moo, AU - Kim,Yong-Jin, AU - Kim,In-San, AU - Kwon,Tae-Hwan, AU - Kim,Yong-Lim, Y1 - 2007/03/27/ PY - 2007/3/29/pubmed PY - 2007/8/8/medline PY - 2007/3/29/entrez SP - 1497 EP - 507 JF - Journal of the American Society of Nephrology : JASN JO - J Am Soc Nephrol VL - 18 IS - 5 N2 - The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/17389738/Erythropoietin_decreases_renal_fibrosis_in_mice_with_ureteral_obstruction:_role_of_inhibiting_TGF_beta_induced_epithelial_to_mesenchymal_transition_ L2 - https://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=17389738 DB - PRIME DP - Unbound Medicine ER -