Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: Role of inhibiting TGF-β-induced epithelial-to-mesenchymal transition

Sun Hee Park, Min Jeong Choi, In Kyung Song, Soon Youn Choi, Ju Ock Nam, Chan Duck Kim, Byung Heon Lee, Rang Woon Park, Moo Park Kwon, Yong Jin Kim, In San Kim, Tae Hwan Kwon, Yong Lim Kim

Research output: Contribution to journalArticle

69 Citations (Scopus)

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-β1-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-β1, α-smooth muscle actin (α-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-β1 and α-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-β1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-β1 and rhEPO for another 48 h. Increased expressions of α-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-β1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-β1 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-β1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-β1-induced EMT.

Original languageEnglish
Pages (from-to)1497-1507
Number of pages11
JournalJournal of the American Society of Nephrology
Volume18
Issue number5
DOIs
Publication statusPublished - 2007 May
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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