The impact of purinergic signaling on renal ischemia-reperfusion injury

Lu, Bo, Rajakumar, Siddharth V, Robson, Simon C, Lee, Eddy K F, Crikis, Sandra, D'Apice, Anthony J F, Cowan, Peter J and Dwyer, Karen M 2008, The impact of purinergic signaling on renal ischemia-reperfusion injury, Transplantation, vol. 86, no. 12, pp. 1707-1712, doi: 10.1097/TP.0b013e31819022bc.

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Title The impact of purinergic signaling on renal ischemia-reperfusion injury
Author(s) Lu, Bo
Rajakumar, Siddharth V
Robson, Simon C
Lee, Eddy K F
Crikis, Sandra
D'Apice, Anthony J F
Cowan, Peter J
Dwyer, Karen MORCID iD for Dwyer, Karen M
Journal name Transplantation
Volume number 86
Issue number 12
Start page 1707
End page 1712
Total pages 6
Publisher Lippincott Williams & Wilkins
Place of publication Philadelphia, Pa.
Publication date 2008
ISSN 0041-1337
Keyword(s) CD39
Renal ischemia-reperfusion injury
Summary BACKGROUND.: Adenosine provides renovascular protection in mouse models of ischemia-reperfusion injury (I/RI) through purinergic members of the G protein-coupled receptor family, such as the adenosine 2A receptor (A2AR). Ectonucleotidases CD39 and CD73 are integral vascular and immune nucleotidases that regulate extracellular adenosine signaling. Current investigation of CD39 and CD73 in renal I/RI has primarily focused on their respective roles in ischemic preconditioning. METHODS.: In this study, we established a unilateral renal I/RI model and investigated the role of adenosine generation versus nucleotide removal in mediating protection in renal I/RI using mice deficient in CD39, CD73 or A2AR, thereby sequentially disrupting ectonucleotidase cascade and adenosinergic signaling. RESULTS.: Compared with wild-type mice, Cd73 null mice showed reduced levels of serum creatinine and urea, apoptosis of renal cells, and histologic damage after I/RI. Deletion of CD39 was associated with severe renal injury. Administration of apyrase, a soluble form of CD39, decreased global apoptosis and I/RI induced renal injury in wild-type mice. Apyrase treatment also improved renal histology to some extent in A2AR null mice. CONCLUSION.: The relative protective effect of CD73 deletion in renal I/RI may reflect an effect of AMP accumulation. Deletion of CD39 showed deleterious effects and administration of soluble CD39 exerted renal protection, which is partially mediated by A2AR. The protective effect conferred by apyrase suggests that supplementing CD39 NTPDase activity may be a useful therapeutic strategy in renal transplantation.
Language eng
DOI 10.1097/TP.0b013e31819022bc
Indigenous content off
Field of Research 11 Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
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Document type: Journal Article
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