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) 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 Zhang, G. Articles by Eddy, A. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, G. Articles by Eddy, A. A. Related Collections Related Article

Mitogenic Signaling of Urokinase Receptor–Deficient Kidney Fibroblasts: Actions of an Alternative Urokinase Receptor and LDL Receptor–Related Protein

University of Washington, Children’s Hospital and Regional Medical Center, Division of Nephrology, Seattle, Washington

Correspondence to Dr. Allison A. Eddy, Children’s Hospital and Regional Medical Center, Division of Nephrology, Mail Stop M1-5, 4800 Sand Point Way NE, Seattle, WA 98105. Phone: 206-987-2524; E-mail: allison.eddy{at}seattlechildrens.org

ABSTRACT. The urokinase receptor (uPAR) attenuates myofibroblast recruitment and fibrosis in the kidney. This study examined the role of uPAR and its co-receptor LDL receptor-related protein (LRP) in the regulation of kidney fibroblast proliferation and extracellular signal-regulated kinase (ERK) signaling. Compared with uPAR+/+ cells, uPAR–/– kidney fibroblasts were hyperproliferative. UPAR–/– fibroblast proliferation was 60% inhibited by an ERK kinase inhibitor. LRP protein was reduced and extracellular accumulation of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) proteins were greater in uPAR–/– cultures. Addition of functional uPA protein or LRP antisense RNA significantly increased ERK signaling and cell mitosis in both genotypes. Enhanced uPAR–/– fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide. The density of cell-bound fluor-uPA was similar between uPAR–/– and uPAR+/+ fibroblasts (78 ± 6 versus 92 ± 16 units). These data suggest that uPAR-deficient kidney fibroblasts express lower levels of its scavenger co-receptor LRP, resulting in greater extracellular accumulation of uPA and PAI-1. Enhanced proliferation of uPAR–/– fibroblasts seems to be mediated by uPA-dependent ERK signaling via an alternative urokinase receptor.

Related Article

This Month’s Highlights
J. Am. Soc. Nephrol. 2004 15: 1967-1970. [Full Text] [PDF]

This article has been cited by other articles:

				I. Yamaguchi, J. M. Lopez-Guisa, X. Cai, S. J. Collins, D. M. Okamura, and A. A. Eddy Endogenous urokinase lacks antifibrotic activity during progressive renal injury Am J Physiol Renal Physiol, July 1, 2007; 293(1): F12 - F19. [Abstract] [Full Text] [PDF]

				G. Zhang, K. A. Kernan, S. J. Collins, X. Cai, J. M. Lopez-Guisa, J. L. Degen, Y. Shvil, and A. A. Eddy Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition: Role of Plasmin-Activated Signals J. Am. Soc. Nephrol., March 1, 2007; 18(3): 846 - 859. [Abstract] [Full Text] [PDF]

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