Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Am Soc Nephrol. 2012 Sep;23(9):1538-50. doi: 10.1681/ASN.2012020137. Epub 2012 Aug 2.

Activation of parenchymal CD47 promotes renal ischemia-reperfusion injury.

Author information

  • 1Division of Pulmonary Allergy and Critical Care Medicine, Vascular Medicine Institute, University of Pittsburgh School of Medicine, E1240 Biomedical Science Tower, Room E1258, 200 Lothrop Street, Pittsburgh, PA 15261, USA.

Abstract

Ischemia-reperfusion injury (IRI) contributes to decreased allograft function and allograft rejection in transplanted kidneys. Thrombospondin-1 is a stress protein typically secreted in response to hypoxia and the ligand activator for the ubiquitously expressed receptor CD47. The function of activated CD47 in IRI remains completely unknown. Here, we found that both CD47 and its ligand thrombospondin-1 were upregulated after renal IRI in mice. CD47-knockout mice were protected against renal dysfunction and tubular damage, suggesting that the development of IRI requires intact CD47 signaling. Chimeric CD47-knockout mice engrafted with wild-type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild-type controls after IRI, suggesting that CD47 signaling in parenchymal cells predominantly mediates renal damage. Treatment with a CD47-blocking antibody protected mice from renal dysfunction and tubular damage compared with an isotype control. Taken together, these data imply that CD47 on parenchymal cells promotes injury after renal ischemia and reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent or suppress ischemia-reperfusion-mediated damage.

PMID:
22859854
[PubMed - indexed for MEDLINE]
PMCID:
PMC3431420
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk