RETRACTED: Signaling through hepatocellular A2B adenosine receptors dampens ischemia and reperfusion injury of the liver

• DOI: 10.1073/pnas.1221733110
• Publication Date: 2013-06-29T07:27:30Z
• Authors: Michael A. Zimmerman; Almut Grenz; Eunyoung Tak; Maria Kaplan; Douglas Ridyard; Kelley S. Brodsky; Mercedes Susan Ma...; Igal Kam; Holger K. Eltzschig
• Keywords: Adenosine A2B receptor; Ischemic Preconditioning; Adenosine A3 receptor

Ischemia and reperfusion significantly contributes to the morbidity mortality of liver surgery transplantation. Based on studies showing a critical role for adenosine signaling in mediating tissue adaptation during hypoxia, we hypothesized that events through receptors (ADORA1, ADORA2A, ADORA2B, or ADORA3) attenuates hepatic ischemia injury. Initial screening human biopsies obtained transplantation demonstrated selective robust induction ADORA2B transcript protein following reperfusion. Subsequent exposure gene-targeted mice each individual receptor revealed Adora2b protection. Moreover, treatment wild-type with an Adora2b-selective antagonist resulted enhanced injury, whereas Adora2b-agonist was associated attenuated injury wild-type, but not −/− mice. deletion different tissues—including vascular endothelia, myeloid cells, hepatocytes—revealed surprising hepatocellular-specific attenuating nuclear factor NF-κB activation thereby protection from These provide unique