Protective role of ecto-5′-nucleiotidase (CD73) in renal ischemia

Almut Grenz, Hua Zhang, Tobias Eckle, Michel Mittelbronn, Manfred Wehrmann, Christoph Köhle, Doris Kloor, Linda F. Thompson, Hartmut Osswald*, Holger K. Eltzschig

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

138 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)833-845
Number of pages13
JournalJournal of the American Society of Nephrology : JASN
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

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