Journal
TRANSPLANTATION
Volume 86, Issue 12, Pages 1707-1712Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31819022bc
Keywords
CD39; CD73; Adenosine; A(2A) receptor; Renal ischemia-reperfusion injury
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia [447706]
- Genzyme Renal Innovations Program
- National Institutes of Health (NIH) of USA
Ask authors/readers for more resources
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 (A(2A)R). Ectonucleotidases CD39 and CD73 arc 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 renil 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 A(2A)R, 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 A(2A)R 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 A(2A)R. The protective effect conferred by apyrase suggests that supplementing CD39 NTPDase activity may be a useful therapeutic strategy in renal transplantation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available