Analysis of potential immune-related genes involved in the pathogenesis of ischemia-reperfusion injury following liver transplantation

Front Immunol. 2023 Mar 16:14:1126497. doi: 10.3389/fimmu.2023.1126497. eCollection 2023.

Abstract

Background: Hepatic ischemia-reperfusion (I/R) injury is an unavoidable pathological process that occurs after liver transplantation. However, the immune-related molecular mechanism still remains unclear. This study aims to further explore the biological mechanisms of immune-related genes in hepatic I/R injury.

Methods: Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the differentially expressed genes (DEGs) were taken for intersection. After identifying common DEGs, functional annotation, protein-protein interaction (PPI) network, and modular construction were performed. The immune-related hub genes were obtained, which their upstream transcription factors and non-RNAs were predicted. Validation of the hub genes expression and immune infiltration were performed in a mouse model of hepatic I/R injury.

Results: A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480). The GO and KEGG enrichment analysis results indicated that immune and inflammatory response played an important role in hepatic I/R injury. Finally, 9 immune-related hub genes were identified by intersecting cytoHubba with immune-related genes, including SOCS3, JUND, CCL4, NFKBIA, CXCL8, ICAM1, IRF1, TNFAIP3, and JUN.

Conclusion: Our study revealed the importance of the immune and inflammatory response in I/R injury following liver transplantation and provided new insights into the therapeutic of hepatic I/R injury.

Keywords: differentially expressed genes; hub genes; immune; ischemia-reperfusion injury; liver transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Profiling / methods
  • Liver Transplantation* / adverse effects
  • Mice
  • Protein Interaction Maps / genetics
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / metabolism
  • Transcriptome

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81870067; No. 82170664) and Wuhan Science and Technology Bureau (No.2020020601012213).