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.2006060677v1 17/12/3374    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 Flamant, M. Articles by Dussaule, J.-C. Search for Related Content PubMed PubMed Citation Articles by Flamant, M. Articles by Dussaule, J.-C.

Discoidin Domain Receptor 1 Null Mice Are Protected against Hypertension-Induced Renal Disease

Martin Flamant^*, Sandrine Placier^*, Anita Rodenas, Cyrile Anne Curat, Wolfgang F. Vogel, Christos Chatziantoniou^* and Jean-Claude Dussaule^*,||

^* INSERM U702, Tenon Hospital, Pierre et Marie Curie University, Department of Pathology, Tenon Hospital, and ^|| AP-HP, Department of Physiology, School of Medicine St. Antoine, Pierre et Marie Curie University, Paris, France; Institute of Cardiovascular Physiology, J.W. Goethe University, Frankfurt, Germany; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Address correspondence to: Dr. Christos Chatziantoniou, INSERM U702, Hopital Tenon, 4 rue de la Chine, Paris 75020, France. Phone: +331-5601-6653; Fax: +331-4364-5448; E-mail: christos.chatziantoniou{at}tnn.ap-hop-paris.fr

Received for publication June 29, 2006. Accepted for publication September 12, 2006.

A frequent complication of hypertension is the development of chronic renal failure. This pathology usually is initiated by inflammatory events and is characterized by the abnormal accumulation of collagens within the renal tissue. The purpose of this study was to investigate the role of discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor that displays tyrosine-kinase activity, in the development of renal fibrosis. To this end, hypertension was induced with angiotensin in mice that were genetically deficient of DDR1 and in wild-type controls. After 4 or 6 wk of angiotensin II administration, wild-type mice developed hypertension that was associated with perivascular inflammation, glomerular sclerosis, and proteinuria. Systolic pressure increase was similar in the DDR1-deficient mice, but the histologic lesions of glomerular fibrosis and inflammation were significantly blunted and proteinuria was markedly prevented. Immunostaining for lymphocytes, macrophages, and collagens I and IV was prominent in the renal cortex of wild-type mice but substantially reduced in DDR1 null mice. In separate experiments, renal cortical slices of DDR1 null mice showed a blunted response of chemokines to LPS that was accompanied by a considerable protection against the LPS-induced mortality. These results indicate the importance of DDR1 in mediating inflammation and fibrosis. Use of DDR1 inhibitors could provide a completely novel therapeutic approach against diseases that have these combined pathologies.

This article has been cited by other articles:

				C. Franco, G. Hou, P. J. Ahmad, E. Y.K. Fu, L. Koh, W. F. Vogel, and M. P. Bendeck Discoidin Domain Receptor 1 (Ddr1) Deletion Decreases Atherosclerosis by Accelerating Matrix Accumulation and Reducing Inflammation in Low-Density Lipoprotein Receptor-Deficient Mice Circ. Res., May 23, 2008; 102(10): 1202 - 1211. [Abstract] [Full Text] [PDF]

				A. D. Konitsiotis, N. Raynal, D. Bihan, E. Hohenester, R. W. Farndale, and B. Leitinger Characterization of High Affinity Binding Motifs for the Discoidin Domain Receptor DDR2 in Collagen J. Biol. Chem., March 14, 2008; 283(11): 6861 - 6868. [Abstract] [Full Text] [PDF]

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