Bioinformatis analysis reveals possible molecular mechanism of PXR on regulating ulcerative colitis

Abstract

AbstractInflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal (GI) tract. Ulcerative colitis (UC) is a type of IBD. Pregnane X Receptor (PXR) is a member of the nuclear receptor superfamily. In order to deepen understanding and exploration of the molecular mechanism of regulation roles of PXR on UC, biological informatics analysis was performed. First, 878 overlapping differentially expressed genes (DEGs) between UC and normal samples were obtained from the Gene Expression Omnibus (GEO) database (GSE59071 and GSE38713) by using the "limma" R language package. Then WGCNA analysis was performed by 878 DEGs to obtain co-expression modules that were positively and negatively correlated with clinical traits. GSEA analysis of PXR results obtained the signal pathways enriched in the PXR high and low expression group and the active genes of each signal pathway. Then the association of PXR with genes that are both active in high expression group and negatively related to diseases (gene set 1), or both active in low expression group and negatively related to diseases (gene set 2) was analyzed by String database. Finally, carboxylesterase 2 (CES2), ATP binding cassette subfamily G member 2 (ABCG2), phosphoenolpyruvate carboxykinase (PCK1), PPARG coactivator 1 alpha (PPARGC1A), cytochrome P450 family 2 subfamily B member 6 (CYP2B6) from gene set 1 and C-X-C motif chemokine ligand 8 (CXCL8) from gene set 2 were screened out. After the above analysis and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) verification, we speculated that PXR may exert a protective role on UC by promoting CES2, ABCG2, PCK1, PPARGC1A, CYP2B6 expression and inhibiting CXCL8 expression in their corresponding signal pathway in intestinal tissue.