1. Academic Validation
  2. Connexin 32 deficiency protects the liver against ischemia/reperfusion injury

Connexin 32 deficiency protects the liver against ischemia/reperfusion injury

  • Eur J Pharmacol. 2020 Jun 5;876:173056. doi: 10.1016/j.ejphar.2020.173056.
Shan Wu 1 Weifeng Yao 1 Chaojin Chen 1 Huixin Chen 1 Fei Huang 1 Yiqian Liu 2 Jun Cai 3 Dongdong Yuan 4 Ziqing Hei 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
  • 2 Southern Medical University, Guangzhou, 510515, China.
  • 3 Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. Electronic address: [email protected].
  • 4 Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. Electronic address: [email protected].
  • 5 Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. Electronic address: [email protected].
Abstract

Hepatic ischemia/reperfusion (I/R) injury is a common complication in the clinical setting. Our previous study has shown that connexin 32 (Cx32) plays a major role in renal I/R injury; however, the role of Cx32 in hepatic I/R injury remains unknown. Liver tissue and serum samples from patients undergoing orthotopic liver transplantation (OLT) were used to evaluate the function of Cx32 in OLT post-reperfusion injury. Then, partial hepatic ischemia was established in global Cx32 knockout mice and wild-type mice followed by reperfusion. Hepatic injury markers were examined. Cx32 small interfering RNA and the p53 inhibitor, pifithrin-α, tenovin-1 were used to examine the relationship between Cx32 and the p53/puma pathways in the BRL-3A and murine primary hepatocytes hypoxia/reoxygenation (H/R) model. Corresponding to liver damage, Cx32 was significantly induced both during OLT in human patients and partial hepatic I/R in mice. Cx32 KO mice exhibited less liver injury than controls. Cx32 deficiency significantly suppressed the p53/puma pathways and hepatocyte Apoptosis. Similar results were observed in the BRL-3A and murine primary hepatocytes H/R model. Propofol protected against OLT post-reperfusion injury and hepatocyte Apoptosis by inhibiting Cx32. In conclusion Cx32 is a novel regulator of hepatic I/R injury through the modulation of hepatocyte Apoptosis and damage, largely via the p53/puma signaling pathway.

Keywords

Apoptosis; Connexin 32; Hepatic ischemia/reperfusion injury; Propofol; p53/puma.

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