The research development of STAT3 in hepatic ischemia-reperfusion injury

Abstract

Ischemia-reperfusion injury (IRI) is a common complication of surgery, which can cause rapid deterioration of the liver function, increase the risk of graft rejection, and seriously affect the prognosis of patients. The signal transducer and activator of transcription 3 (STAT3) protein has been implicated in pathogenesis of IRI. STAT3 influences the mitochondria through multiple pathways and is also involved in apoptosis and other forms of programmed cell death. STAT3 is associated with Janus kinase (JAK), phosphoinositide-3 kinase (PI3K), and heme oxygenase-1 (HO-1) in liver IRI. The STAT3 pathway plays a dual role in IRI as it can also regulate lipid metabolism which may have potential for treating IRI fatty liver. In this review, we summarize research on the function of STAT3 in liver IRI to provide references for its application in the clinic.

SYK Promotes the Formation of Neutrophil Extracellular Traps by Inducing PKM2 Nuclear Translocation and Promoting STAT3 Phosphorylation to Exacerbate Hepatic Ischemia-Reperfusion Injury and Tumor Recurrence

“…Administration of SYK inhibitor before IR in mice resulted in activation of PKM2 and P-STAT3 and downregulation of their nuclear expression in the injured liver.Nuclear PKM2 has been demonstrated to bind P-STAT3 and promote STAT3 phosphorylation, thereby regulating the expression of in ammatory genes and the production of pro-in ammatory cytokines in a variety of cells [29,30]. STAT3 is a crucial participant in hepatic in ammation, and the role of activated STAT3 in hepatic IRI has been extensively studied [41].In a mouse model of hepatic IRI,pharmacologic inhibition of PKM2 nuclear translocation by TEPP-46 resulted in inhibition of STAT3 activation in neutrophils. These evidences suggest that SYK regulates NETs formation via the neutrophil PKM2/P-STAT3 pathway.…”

Maternal and Fetal Outcomes in Women Receiving Ursodeoxycholeic Acid (Udca) as Treatment for Intrahepatic Cholestasis of Pregnancy (Ihcp), a Single Center Experience: Are We Doing Enough?

“…Many mutations have been seen over the years affecting the bile acid excretion levels. Up to 10 different MDR3 mutations have been identified, and any one of these mutations may result in loss of function and raise bile acid levels (Ayyash et al, 2021;Ferrando et al, 2020;Khunweeraphong and Kuchler, 2021;Yang et al, 2023). There have been associations with progressive familial intrahepatic cholestasis as it has a similar gene mutation (Awanti Jr et al, 2023;Bosma et al, 2020).…”