SP1-Dependent Induction of CD39 Facilitates Hepatic Ischemic Preconditioning

摘要: Ischemia/reperfusion injury (IRI) of the liver is an important cause hepatic dysfunction. Ischemic preconditioning (IP) associated with adenosine-mediated tissue protection from subsequent IRI. Extracellular nucleotides (e.g., ATP) represent main source for extracellular adenosine. Therefore, we hypothesized that phosphohydrolysis ATP/ADP via ectonucleoside triphosphate diphosphohydrolase-1 (CD39), conversion to AMP, mediates IP-dependent protection. We found IP was significant induction CD39 transcript, heightened protein expression, and improved outcomes after Targeted gene deletion or pharmacological inhibition abolished hepatoprotection by as measured serum markers histology. Therapeutic studies mimic i.p. apyrase (a soluble diphosphohydrolase, NTPDase) in absence attenuated In additional vivo studies, small interfering RNA treatment used achieve repression transcription factor Sp1, known be implicated transcriptional regulation. fact, Sp1 increased vivo. Our data suggest a Sp1-dependent regulatory pathway during IP. These reveal novel role ischemia.