1. Academic Validation
  2. IL-22 Protects against Biliary Ischemia-Reperfusion Injury after Liver Transplantation via Activating STAT3 and Reducing Apoptosis and Oxidative Stress Levels In Vitro and In Vivo

IL-22 Protects against Biliary Ischemia-Reperfusion Injury after Liver Transplantation via Activating STAT3 and Reducing Apoptosis and Oxidative Stress Levels In Vitro and In Vivo

  • Oxid Med Cell Longev. 2022 May 10;2022:9635075. doi: 10.1155/2022/9635075.
Yi Bai  # 1 Hao Wu  # 2 Jinrui Zhang  # 2 Sai Zhang 3 4 Zhixin Zhang 2 Hao Wang 2 Yamin Zhang 1 Zhongyang Shen 4 5 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
  • 2 The First Central Clinical School, Tianjin Medical University, Tianjin, China.
  • 3 School of Medicine, Nankai University, Tianjin, China.
  • 4 Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
  • 5 Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin, China.
  • 6 National Health Commission's Key Laboratory for Critical Care Medicine, Tianjin, China.
  • # Contributed equally.
Abstract

Biliary complications are currently one of the leading causes of liver failure and patient death after liver transplantation and need to be solved urgently. Biliary ischemia-reperfusion injury (IRI) is one of the important causes of biliary complications. IL-22 has a protective effect on liver injury and hepatitis diseases, and its safety and efficacy in the treatment of hepatitis have also been proved in human clinical experiments. Furthermore, multiple studies have confirmed that IL-22 promotes the proliferation and repair of epithelial cells in various organs. Still, its function in the bile duct after transplantation has not been explored. This study was aimed at investigating the effects of IL-22 on cholangiocyte IRI in vitro and in vivo and exploring its underlying mechanisms. We simulated the hypoxia process of bile duct epithelial cells through in vitro experiments to investigate the protective function and molecular mechanism of IL-22 on bile duct epithelial cells. Subsequently, the function and mechanism of IL-22 in the biliary IRI model of autologous orthotopic liver transplantation in rats were assessed. This study confirmed that IL-22 could promote cholangiocyte proliferation, decrease the Apoptosis rate of cholangiocytes and tissues, decrease MDA levels, and increase SOD levels by activating STAT3. In addition, IL-22 can also reduce the level of mitochondrial membrane depolarization, protect mitochondria, reduce ROS production, and play a role in protecting bile ducts. These findings provide evidence for IL-22 as a novel and effective treatment for biliary IRI after liver transplantation.

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