2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005080866v1 18/5/1497    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, S.-H. Articles by Kim, Y.-L. Search for Related Content PubMed PubMed Citation Articles by Park, S.-H. Articles by Kim, Y.-L.

Erythropoietin Decreases Renal Fibrosis in Mice with Ureteral Obstruction: Role of Inhibiting TGF-–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, Kwon Moo Park, Yong-Jin Kim, In-San Kim, Tae-Hwan Kwon and Yong-Lim Kim^*

^* Division of Nephrology and Department of Internal Medicine, Department of Biochemistry and Cell Biology, and Department of Anatomy, Kyungpook National University School of Medicine, and Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea

Address correspondence to: Dr. Yong-Lim Kim, Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital, 50 Samduk-dong 2Ga, Jung-gu, Daegu 700-721, Korea. Phone: +82-53-420-5553; Fax: +82-53-423-7583; E-mail: ylkim{at}knu.ac.kr or Dr. Tae-Hwan Kwon, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 700-422 Korea. Phone: +82-53-420-4825, Fax: +82-53-422-1466; E-mail: thkwon{at}knu.ac.kr

Received for publication August 19, 2005. Accepted for publication February 3, 2007.

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

This article has been cited by other articles:

				J.-H. Kie, M. H. Kapturczak, A. Traylor, A. Agarwal, and N. Hill-Kapturczak Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1681 - 1691. [Abstract] [Full Text] [PDF]

				P. Boor, K. Sebekova, T. Ostendorf, and J. Floege Treatment targets in renal fibrosis Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3391 - 3407. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673