Protective Role of Ecto-5'-Nucleotidase (CD73) in Renal Ischemia

A. Grenz, H. Zhang, T. Eckle, M. Mittelbronn, M. Wehrmann, C. Kohle, D. Kloor, L. F. Thompson, H. Osswald, H. K. Eltzschig
2007 Journal of the American Society of Nephrology  
Acute renal failure from ischemia significantly contributes to cardiovascular morbidity and mortality. Extracellular adenosine has been implicated as an anti-inflammatory metabolite particularly during conditions of limited oxygen availability (e.g., ischemia). Because ecto-5-nucleotidase (CD73) is rate limiting for extracellular adenosine generation, this study examined the contribution of CD73-dependent adenosine production to ischemic preconditioning (IP) of the kidneys. After the initial
more » ... ervation that murine CD73 transcript, protein, and function are induced by renal IP, its role in IP-mediated kidney protection was studied. In fact, increases in renal adenosine concentration with IP are attenuated in cd73 Ϫ/Ϫ mice. Moreover, pharmacologic inhibition of CD73 or its targeted gene deletion abolished renal protection by IP as measured by clearance studies, plasma electrolytes, and renal tubular destruction, and reconstitution of cd73 Ϫ/Ϫ mice with soluble 5-nucleotidase resulted in complete restoration of renal protection by IP. Finally, renal injury after ischemia was attenuated by intraperitoneal treatment of wild-type mice with soluble 5-nucleotidase to a similar degree as by IP. Taken together, these data reveal what is believed to be a previously unrecognized role of CD73 in renal protection from ischemia and suggest treatment with soluble 5-nucleotidase as a novel therapeutic approach in the treatment of renal diseases that are precipitated by limited oxygen availability.
doi:10.1681/asn.2006101141 pmid:17267736 fatcat:dyyxl5ftsffm7ajlwzpzkisbiu