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

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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Upregulated SSB Is Involved in Hepatocellular Carcinoma Progression and Metastasis through the Epithelial-Mesenchymal Transition, Antiapoptosis, and Altered ROS Level Pathway

“…Then, the cells were incubated at room temperature in the dark for 15 min. Finally, the level of apoptosis was detected by flow cytometry (BD Accuri C6 Plus, USA) [ 20 ]. Data were processed using FlowJo (V10.0) software.…”

DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome

“…The cells were resuspended in phosphate-buffered saline and analysed using the DNA content quantitation assay (Cell Cycle; CA1510, Solarbio). In addition, changes in the levels of reactive oxygen species, mitochondrial membrane potential, and apoptosis in D-gal-treated cells were detected using the corresponding kits, including a Reactive Oxygen Species Assay Kit (CA1410, Solarbio) ( 42 ), Mitochondrial Membrane Potential Assay Kit with JC-1(M8650, Solarbio) ( 43 ), and Annexin V-FITC apoptosis detection kit (A005-3,7 Sea Pharmatech, Shanghai, China) ( 44 ). A flow cytometry system (BD LSR Fortessa, Indianapolis, NJ, USA) was used to analyse the results of these four tests.…”