Protective role of ecto-5'-nucleotidase (CD73) in renal ischemia.

Abstract

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 observation 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(-/-) 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(-/-) 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.

• Authors: Almut Grenz, Hua Zhang, Tobias Eckle, Michel Mittelbronn, Manfred Wehrmann, Christoph Köhle, Doris Kloor, Linda F Thompson, Hartmut Osswald, Holger K Eltzschig
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 18 Issue 3 Pg. 833-45 (Mar 2007) ISSN: 1046-6673 [Print] United States
• PMID: 17267736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 5'-Nucleotidase
• Adenosine

Topics

• 5'-Nucleotidase (deficiency, genetics, metabolism)
• Acute Kidney Injury (etiology, prevention & control)
• Adenosine (biosynthesis)
• Animals
• Disease Models, Animal
• Ischemia (complications, metabolism)
• Ischemic Preconditioning
• Kidney (blood supply, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout