Abstract
Inflammatory 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.
Highlights
Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal (GI) tract
In order to deeply explore the molecular mechanism of Pregnane X Receptor (PXR) on Ulcerative colitis (UC) regulation, integrated bioinformatics methods were used in this study
As PXR expression level is low in UC disease and has a protective role on UC, PXR may protect UC by positively regulating the signal pathway enriched in the high expression group or negatively regulating the signal pathway enriched in the low expression group
Summary
GSE59071, the platform is the [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array, which includes 74 UC samples and 11 normal. Based on the initial data, we utilized the "limma" R package in R to screen the DEGs between UC samples and normal samples. WGCNA is a systematic biological method for constructing scale-free networks using gene expression data. The expression data profile of the overlapping DEGs in GSE59071 was tested to see whether they were suitable samples and genes. STRING (version 11.0) database (https:// string-db.org)[25] was used to build the PPI network (score > 0.4) and the protein that interacted and associated with PXR was screened out. Pearson’s correlation coefficients (R-values) between the expression levels of PXR and the other genes were analyzed by the "Pearson" method in R Studio.
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