Canonical notch pathway protects hepatocytes from ischemia/reperfusion injury in mice by repressing reactive oxygen species production through JAK2/STAT3 signaling

• DOI: 10.1002/hep.24469
• Publication Date: 2011-06-03T09:14:19Z
• Authors: Heng-Chao Yu; Hong-Yan Qin; Fei He; Lin Wang; Wei Fu; Dong Liu; Feng-Cheng Guo; Liang Liang; Ke-Feng Dou; Hua Han
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; Receptors, Notch; Superoxide Dismutase; Apoptosis; Janus Kinase 2; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver; Cytoprotection; Reperfusion Injury; Hepatocytes; Animals; Reactive Oxygen Species; Cells, Cultured; Signal Transduction

Hepatic ischemia/reperfusion (I/R) injury is initiated by reactive oxygen species (ROS) accumulated during the early reperfusion phase after ischemia, but cellular mechanisms controlling ROS production and scavenging have not been fully understood. In this study, we show that blocking Notch signal knockout of transcription factor RBP-J or a pharmacological inhibitor led to aggravated hepatic I/R injury, as manifested deteriorated liver function increased apoptosis, necrosis, inflammation, both in vitro vivo. Interruption signaling resulted intracellular hepatocytes, scavenger cured exacerbated blockade, suggesting deficiency through levels. blockade down-regulation Hes5, leading reduced formation Hes5-STAT3 complex hypophosphorylation STAT3, which further attenuated manganese superoxide dismutase (MnSOD) expression apoptosis. Indeed, overexpression constitutively active STAT3 rescued MnSOD injury-induced apoptosis absence signaling. Finally, forced activation ligand stimulation Hes5 protected hepatocytes from expression.Notch protects Hes5-dependent activates MnSOD, ROS.