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) 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 Bengatta, S. Articles by Lelongt, B. Search for Related Content PubMed PubMed Citation Articles by Bengatta, S. Articles by Lelongt, B. Related Collections Related Article

MMP9 and SCF Protect from Apoptosis in Acute Kidney Injury

Soraya Bengatta^*,, Catherine Arnould^*,, Emmanuel Letavernier^*,, Matthieu Monge^*,, Hélène Martinan de Préneuf^*,, Zena Werb, Pierre Ronco^*,, and Brigitte Lelongt^*,

^* UPMC University of Paris 06, INSERM, UMR S 702, and AP-HP, Hôpital Tenon, Paris, France; and Department of Anatomy, University of California, San Francisco, San Francisco, California

Correspondence: Dr. Brigitte Lelongt, INSERM UMR S 702, Hôpital Tenon, 4 rue de la Chine, 75970 Paris cedex 20, France. Phone: 33-1-56-01-65-14; Fax: 33-1-56-01-65-12; E-mail: brigitte.lelongt{at}chusa.jussieu.fr

Received for publication May 20, 2008. Accepted for publication November 18, 2008.

Apoptosis of tubular epithelial cells is a hallmark of acute kidney injury (AKI), but the cellular events preceding apoptosis in this setting are incompletely understood. Because matrix metalloproteinase 9 (MMP9) degrades matrix components involved in cell survival, we studied the role of MMP9 in AKI. In the mouse model of folic acid–induced AKI, we observed a marked increase of MMP9 activity in the S3 segment of the proximal tubule (S3PT), correlating with the apoptotic phase. MMP9 deficiency increased apoptosis and the severity of renal lesions and substantially delayed recovery of renal function. MMP9–/– mice exhibited significant apoptosis in the S3PT and the intercalated cells of the collecting duct (I-CD), whereas wild-type mice exhibited none in these segments. Stem cell factor (SCF), an MMP9 substrate, was identified in the S3PT, and its receptor, c-Kit, was expressed in both the S3PT and I-CD. MMP9 released the soluble form of SCF (sSCF) from kidney cells in vivo and in vitro. In addition, SCF inhibited apoptosis of tubular cells in vitro, rescued MMP9–/– S3PT and I-CD from apoptosis in vivo, and improved renal function. An ischemia-reperfusion model of AKI produced similar results. In patients with AKI, urinary sSCF increased with acute tubular necrosis but not with prerenal azotemia. In conclusion, these data show that MMP9 protects the S3 segment of the proximal tubule and the I-CD from apoptosis in AKI, most likely by releasing sSCF.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2009 20: A12. [Full Text] [PDF]

This article has been cited by other articles:

				C. Arnould, M. Lelievre-Pegorier, P. Ronco, and B. Lelongt MMP9 Limits Apoptosis and Stimulates Branching Morphogenesis During Kidney Development J. Am. Soc. Nephrol., October 1, 2009; 20(10): 2171 - 2180. [Abstract] [Full Text] [PDF]

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