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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1273    most recent 00204.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hammerschmidt, E. Articles by Wolf, G. PubMed PubMed Citation Articles by Hammerschmidt, E. Articles by Wolf, G.

Morg1 heterozygous mice are protected from acute renal ischemia-reperfusion injury

Klinik für Innere Medizin III, Friedrich-Schiller-University, Jena, Germany

Submitted April 10, 2009 ; accepted in final form September 1, 2009

Renal ischemia and reperfusion injury leads to acute renal failure when proinflammatory and apoptotic processes in the kidney are activated. The increase in hypoxia-inducible transcription factor- (HIF-), an important transcription factor for several genes, can attenuate ischemic renal injury. We recently identified a novel WD-repeat protein designated Morg1 (MAPK organizer 1) that interacts with prolyl hydroxylase 3 (PHD3), an important enzyme involved in the regulation of HIF-1 and HIF-2 expression. While homozygous Morg1 –/– mice are embryonic lethal, heterozygous Morg1 +/– mice have a normal phenotype. We show here that Morg1 +/– were partially protected from renal ischemia-reperfusion injury compared with wild-type Morg1 +/+ animals. Morg1 +/– mice compared with wild-type animals revealed a stronger increase in HIF-1 and HIF-2 expression in the ischemic-reperfused kidney associated with enhanced serum erythropoietin levels. However, no significant expression of HIF-1 and HIF-2 was found in nonischemic kidneys without any difference between Morg1 +/– and Morg1 +/+ mice. Ischemic kidneys of Morg1 +/– mice expressed more erythropoietin mRNA than ischemic kidneys from wild-type animals. Renal ischemia in Morg1 +/– mice resulted in a decrease in renal inflammation and reduction of proinflammatory cytokines (MCP-1, IP-10, MIP-2) compared with wild-type mice. Furthermore, there was significantly less apoptosis and tubular damage in Morg1 +/– kidneys after ischemia-reperfusion, and this was also reflected in significantly improved renal function compared with wild-type. Thus Morg1 may be a novel therapeutic target to limit renal injury after ischemia-reperfusion.

hypoxia; HIF-1; HIF-2; renal inflammation; chemokine expression; ischemic renal failure