Identification of key immune-related genes associated with LPS/D-GalN-induced acute liver failure in mice based on transcriptome sequencing.

ABSTRACT

Background: The aim of this study was to identify key immune-related genes in acute liver failure (ALF) by constructing an ALF mouse model for transcriptome sequencing. Methods: The C57BL/6 mouse with ALF model was induced by lipopolysaccharide (LPS)/ D-galactosamine (D-GalN). After successful modelling, the liver tissues of all mice were obtained for transcriptome sequencing. The key immune-related genes in mice with ALF were identified by differential expression analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), enrichment analysis, and protein-protein interaction (PPI) analysis. Results: An LPS/D-GalN-induced ALF mouse model was successfully constructed, and transcriptome sequencing was performed. Significant differences in the proportions of monocytes, macrophages M0, macrophages M1 and neutrophils were shown by immune infiltration analysis, and 5255 genes highly associated with these four immune cells were identified by WGCNA. These immune genes were found to be significantly enriched in the TNF signalling pathway by enrichment analysis. Finally, PPI analysis was performed on genes enriched in this pathway and three key genes (CXCL1, CXCL10 and IL1B) were screened out and revealed to be significantly upregulated in ALF. Conclusions: Key immune-related genes in ALF were identified in this study, which may provide not only potential therapeutic targets for treating ALF and improving its prognosis, but also a reliable scientific basis for the immunotherapy of the disease.