Investigating the expression of CD180, LY96, VCAM-1, and CSF2RB in the lipopolysaccharide response pathway across different liver cirrhosis etiologies.

BACKGROUND

Liver cirrhosis represents a significant global health burden with diverse etiological factors. The lipopolysaccharide response pathway is critical in liver disease development. This study investigates this pathway in liver cirrhosis associated with various etiologies, including nonalcoholic steatohepatitis, alcohol consumption, viral infections, autoimmune disorders, and cholestatic disorders.

METHODS AND RESULTS

The GSE25097 and GSE54238 microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database using R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the overlapping Differentially Expressed Genes (DEGs). Gene expression was determined by RT-qPCR, and protein expression was determined by Western blot. A total of 499 overlapping DEGs were identified between the two datasets. Then, the GOBP enrichment analysis subsequently discovered the lipopolysaccharide response pathway, highlighting genes such as CD180, LY96, VCAM-1, and CSF2RB. Based on bioinformatics analysis, the expressions of all mentioned genes were elevated in cirrhotic samples. However, experimental results showed an increase only in CD180 gene expression. Our research has shown that the expressions of the LY96, VCAM-1, and CSF2RB genes were elevated only in PSC cirrhosis. The PSC group had an elevation in LY96 protein expression. On the other hand, all the gene expressions significantly decreased in NASH cirrhosis, although only the VCAM-1 protein expression was reduced in NASH cirrhosis.

CONCLUSIONS

The response to the lipopolysaccharide pathway has a complicated role in liver disease pathogenesis. While gene expression of pathway components increases in cholangitis-related cirrhosis, it decreases in NASH-associated cirrhosis.