Journal of the American Society of Nephrology
2008 JASN IMPACT FACTOR 7.505 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


Published ahead of print on April 23, 2009
J Am Soc Nephrol 20: 1275-1281, 2009
© 2009 American Society of Nephrology
doi: 10.1681/ASN.2008060559
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
ASN.2008060559v1
20/6/1275    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Taylor, S. R.J.
Right arrow Articles by Tam, F. W.K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taylor, S. R.J.
Right arrow Articles by Tam, F. W.K.

BASIC RESEARCH

P2X7 Deficiency Attenuates Renal Injury in Experimental Glomerulonephritis

Simon R.J. Taylor*, Clare M. Turner{dagger},{ddagger}, James I. Elliott§, John McDaid{dagger}, Reiko Hewitt{dagger}, Jennifer Smith{dagger}, Matthew C. Pickering§, Darren L. Whitehouse||, H. Terence Cook, Geoffrey Burnstock**, Charles D. Pusey{dagger}, Robert J. Unwin{ddagger} and Frederick W.K. Tam{dagger}

* MRC Clinical Sciences Centre, {dagger} Imperial College Kidney and Transplant Institute, and § Department of Molecular Genetics and Rheumatology, Division of Medicine, and Department of Pathology, Division of Investigative Science, Imperial College London, and {ddagger} Centre for Nephrology and ** Autonomic Neuroscience Centre, University College London (Royal Free Campus), London, United Kingdom; and || Department of Chemistry, Institutes for Pharmaceutical Discovery, LLC, Branford, Connecticut

Correspondence: Dr. Frederick W.K. Tam, Imperial College Kidney and Transplant Institute, Division of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12, UK. Phone: 020-8383-2354; Fax: 020-8383-2062; E-mail: f.tam{at}imperial.ac.uk

Received for publication June 1, 2008. Accepted for publication January 22, 2009.

The P2X7 receptor is a ligand-gated cation channel that is normally expressed by a variety of immune cells, including macrophages and lymphocytes. Because it leads to membrane blebbing, release of IL-1β, and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of inflammatory diseases. Although the P2X7 receptor is usually not detectable in normal renal tissue, we previously reported increased expression of both mRNA and protein in mesangial cells and macrophages infiltrating the glomeruli in animal models of antibody-mediated glomerulonephritis. In this study, we used P2X7-knockout mice in the same experimental model of glomerulonephritis and found that P2X7 deficiency was significantly renoprotective compared with wild-type controls, evidenced by better renal function, a striking reduction in proteinuria, and decreased histologic glomerular injury. In addition, the selective P2X7 antagonist A-438079 prevented the development of antibody-mediated glomerulonephritis in rats. These results support a proinflammatory role for P2X7 in immune-mediated renal injury and suggest that the P2X7 receptor is a potential therapeutic target.






HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

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