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.2006070759v1 18/5/1516    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 Patschan, D. Articles by Goligorsky, M. S. Search for Related Content PubMed PubMed Citation Articles by Patschan, D. Articles by Goligorsky, M. S.

Uric Acid Heralds Ischemic Tissue Injury to Mobilize Endothelial Progenitor Cells

Daniel Patschan^*, Susann Patschan^*, Glenda G. Gobe, Sreedhar Chintala^* and Michael S. Goligorsky^*

^* Department of Medicine, Renal Research Institute and Division of Nephrology, New York Medical College, Valhalla, New York; and Centre for Kidney Disease Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia

Address correspondence to: Dr. Daniel Patschan or Dr. Michael S. Goligorsky, Department of Medicine, New York Medical College, BSB, R-C21, Valhalla, NY 10595. Phone: 914-594-4731; Fax: 914-594-4732; E-mail: d.patschan{at}gmx.de, michael_goligorsky{at}nymc.edu

Received for publication July 20, 2006. Accepted for publication January 1, 2007.

Understanding the nature of endogenous mechanisms for mobilization of stem/progenitor cells is predicated on the identification of injury-induced substances that are released from a damaged organ and capable of producing a distant effect. Although different substances that mobilize endothelial progenitor cells (EPCs) have been proposed, their potential to signal injury and afford postischemic renoprotection and repair remains obscure. Uric acid (UA) is consistently overproduced by ischemic tissues and has been shown to exert immunomodulatory functions. It was hypothesized that UA and/or its precursors might serve as injury signals that are capable of mobilizing EPCs in acute renal ischemia. Indeed, FVB/NJ mice that were subjected to acute renal ischemia showed a transient surge in UA level in the peripheral blood. Single-dose treatment with UA, as well as acute hyperuricemia induced by the inhibition of uricase, caused a robust mobilization of EPCs, whereas administration of adenosine or inosine seemed to lack this effect. Moreover, pretreatment of mice with a single dose of UA afforded significant renoprotection against ischemic injury. In animals with chronic hyperuricemia (induced by continuous 2-wk treatment with a uricase inhibitor oxonic acid), EPC mobilization was blunted and renoprotective effects were absent. In conclusion, acute elevation of UA acts as "physiologic," fast-acting endogenous mediator of EPC mobilization and renoprotection, consistent with its novel function in pharmacologic preconditioning. Both of these actions are lacking in mice with chronic hyperuricemia. In summary, a transient surge in UA concentration may serve as a universal herald of tissue injury to accelerate the recruitment of EPCs.

This article has been cited by other articles:

				M.-C. Kuo, D. Patschan, S. Patschan, L. Cohen-Gould, H.-C. Park, J. Ni, F. Addabbo, and M. S. Goligorsky Ischemia-Induced Exocytosis of Weibel-Palade Bodies Mobilizes Stem Cells J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2321 - 2330. [Abstract] [Full Text] [PDF]

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