2008 JASN IMPACT FACTOR 7.505	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.2008040424v1 20/3/567    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 Yu, M.-A Articles by Kang, D.-H. Search for Related Content PubMed PubMed Citation Articles by Yu, M.-A Articles by Kang, D.-H.

HGF and BMP-7 Ameliorate High Glucose–Induced Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelium

Min-A Yu^*, Kyung-Sook Shin^*, Jung Hye Kim^*, Yong-Il Kim, Soon Sup Chung, Sun-Hee Park, Yong-Lim Kim and Duk-Hee Kang^*

^* Division of Nephrology, Department of Internal Medicine, and Department of General Surgery, Ewha Womans University School of Medicine, Ewha Medical Research Center, Seoul, and Division of Nephrology, Kyungpook National University, Daegu, Korea

Correspondence: Dr. Duk-Hee Kang, Division of Nephrology, Ewha University School of Medicine, 911 Mok-dong Yangchun-ku, Seoul 158-710, Korea. Phone: 82-2-2650-2870; Fax: 82-2-2655-2076; E-mail: dhkang{at}ewha.ac.kr

Received for publication April 25, 2008. Accepted for publication October 9, 2008.

Over time, peritoneal dialysis results in functional and structural alterations of the peritoneal membrane, but the underlying mechanisms and whether these changes are reversible are not completely understood. Here, we studied the effects of high levels of glucose, which are found in the dialysate, on human peritoneal mesothelial cells (HPMCs). We found that high concentrations of glucose induced epithelial-to-mesenchymal transition (EMT) of HPMC, suggested by decreased expression of E-cadherin and increased expression of -smooth muscle actin, fibronectin, and type I collagen and by increased cell migration. Normalization of glucose concentration on day 2 reversed the phenotypic transformation, but the changes were irreversible after 7 d of stimulation with high glucose. In addition, exposure of HPMC to high glucose resulted in a decreased expression of the antifibrotic cytokines, hepatocyte growth factor (HGF) and bone morphogenic protein 7 (BMP-7). Exogenous treatment with HGF resulted in a dosage-dependent prevention of high glucose–induced EMT. Both BMP-7 peptide and gene transfection with an adenoviral vector of BMP-7 also protected HPMCs from EMT. Furthermore, adenoviral BMP-7 transfection decreased peritoneal EMT and ameliorated peritoneal thickening in an animal model of peritoneal dialysis. In summary, high concentrations of glucose induce a reversible EMT of HPMCs, associated with decreased production of HGF and BMP-7. Treatment of HPMCs with HGF or BMP-7 blocks high glucose–induced EMT, and BMP-7 ameliorates peritoneal fibrosis in an animal model of peritoneal dialysis.

This article has been cited by other articles:

				M. Mizutani, Y. Ito, M. Mizuno, H. Nishimura, Y. Suzuki, R. Hattori, Y. Matsukawa, M. Imai, N. Oliver, R. Goldschmeding, et al. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate Am J Physiol Renal Physiol, March 1, 2010; 298(3): F721 - F733. [Abstract] [Full Text] [PDF]

				A. O. Phillips and D. J. Fraser BMP-7 stops TGF-{beta} in peritoneal fibrosis Nephrol. Dial. Transplant., February 14, 2010; (2010) gfq032v1. [Full Text] [PDF]

				J. Loureiro, M. Schilte, A. Aguilera, P. Albar-Vizcaino, M. Ramirez-Huesca, M. L. Perez-Lozano, G. Gonzalez-Mateo, L. S. Aroeira, R. Selgas, L. Mendoza, et al. BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure Nephrol. Dial. Transplant., January 18, 2010; (2010) gfp618v2. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673