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pmid:33686088

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

Hanze Guo · Yan Chi · Naiyu Chi

Scientific reports · 2021 doi:10.1038/s41598-021-83742-8

Paper

complete

Experiment

partial

Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33686088
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science-record
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created_at
2026-11-01T15:41:27Z
updated_at
2026-11-01T22:03:16Z
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paper object · 10 fields
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title
Bioinformatis analysis reveals possible molecular mechanism of PXR on regulating ulcerative colitis.
doi
10.1038/s41598-021-83742-8
pmid
33686088
authors array · 3 items
[0]
Hanze Guo
[1]
Yan Chi
[2]
Naiyu Chi
journal
Scientific reports
year
2021
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.
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Biological signal pathways and active genes in PXR high expression group by GSEA.
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Biological signal pathways and active genes in PXR low expression group by GSEA.
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GSEA associated with PXR
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Biological signal pathways and active genes in PXR low expression group by GSEA.
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Pathway regulated by PXR
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Active genes and their corresponding signal pathways they participate in after PPI analysis with PXR.
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Six genes were screened out that can interact and functionally associate with PXR
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Active genes and their corresponding signal pathways they participate in after PPI analysis with PXR.
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Predicted sequences that PXR bind on the gene promoters listed below with the highest scores.
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The six genes were regulated by PXR
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Predicted sequences that PXR bind on the gene promoters listed below with the highest scores.
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tase quantitative polymerase chain reaction (RT-qPCR) verification, we speculated that PXR may ex
[1]
e quantitative polymerase chain reaction (RT-qPCR) verification, we speculated that PXR may ex
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ike cell isolated from colon carcinoma, were cultured in DMEM containing 10% FBS with penicillin (100
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "Student’s t test was performed to determine statistical differences between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33686088", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Student’s t test was performed to determine statistical differences between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All authors make sure that all data and materials support published claims and comply with field standards.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33686088", "locator": "sections[28] \"notes\" paragraph 1", "quote": "All authors make sure that all data and materials support published claims and comply with field standards."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33686088"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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MSN ICAM1 CDH5 JAM2 NCF2 RASSF5 ITGB2 PECAM1 RHOH MMP9 THY1 CXCR4 VCAM1"], ["VASCULAR_SMOOTH_MUSCLE_CONTRACTION", "− 1.29", "5", "EDNRA CALCRL"], ["CHEMOKINE_SIGNALING_PATHWAY", "− 1.21", "28", "CXCL5 ELMO1 CXCL10 CCL11 CXCR2 CCR1 CCL18 CCL4 CCR7 CXCR4 CXCL9 CXCL6 CCL2 CCL19 CXCL13"], ["SYSTEMIC_LUPUS_ERYTHEMATOSUS", "− 1.16", "16", "C2 HLA-DRA HLA-DMA HLA-DPA1 HLA-DMB CD40 FCGR3B FCGR2C C1R FCGR2A C1S CD86 C3 FCGR2B"], ["B_CELL_RECEPTOR_SIGNALING_PATHWAY", "− 1.14", "10", "PIK3R3 IFITM1 DAPP1 LYN CD81 RAC2 BTK CD79A FCGR2B"], ["CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION", "− 1.14", "44", "CCL3L3 CXCL11 CXCL1 GHR IFNAR2 CD40 IL1B CXCL8 OSMR CSF3R CSF2RB TNFSF13B KDR TNFRSF11B TGFB1 CXCL5 IL10RA IL2RA CXCL10 CCL11 PDGFRB CD27 CXCR2 CCR1 CCL18 CCL4 INHBA CCR7 TNFRSF17 CXCR4 CXCL9 IL7R CXCL6 CCL2 IL24 CCL19 CXCL13"], ["CELL_ADHESION_MOLECULES_CAMS", "− 1.14", "28", "ICAM1 VCAN CDH5 JAM2 ITGB2 PECAM1 ICAM2 SELPLG CD86 PTPRC VCAM1 SELP SELL SELE"], ["FOCAL_ADHESION", "− 1.14", "22", "COL1A1 RAC2 COL3A1 COL4A2 COL1A2 VWF LAMC1 COL6A3 COL5A2 KDR COL4A1 SPP1 THBS2 ITGA5 CAV1 PDGFRB TNC"], ["JAK_STAT_SIGNALING_PATHWAY", "− 1.12", "12", "GHR IFNAR2 OSMR CSF3R CSF2RB IL10RA IL2RA IL7R IL13RA2 IL24"], ["NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION", "− 1.06", "20", "FPR2 C3AR1 FPR1 S1PR1 P2RY13 P2RY8 EDNRA CALCRL"], ["ECM_RECEPTOR_INTERACTION", "− 1.05", "16", "CD44 COL1A1 COL3A1 COL4A2 COL1A2 VWF LAMC1 COL6A3 COL5A2 COL4A1 SPP1 THBS2 ITGA5 TNC"], ["TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY", "− 1.03", "15", "CXCL11 IFNAR2 CD40 IL1B CXCL8 TLR2 CXCL10 SPP1 CCL4 CD86 CTSK CXCL9 LY96"], ["LYSOSOME", "− 1.02", "5", "CTSH LAPTM5 LAMP3 CTSK"], ["ENDOCYTOSIS", "− 1.01", "13", "RAB31 ASAP1 SMAP2 KDR IL2RA CXCR2 CXCR4"], ["CYTOSOLIC_DNA_SENSING_PATHWAY", "− 1.01", "7", "IL1B AIM2 CXCL10 CCL4 IL33"], ["VIRAL_MYOCARDITIS", "− 1.01", "13", "HLA-DRA HLA-DMA HLA-DPA1 HLA-DMB CD40 RAC2 ICAM1 ITGB2 CAV1 CD86"], ["LEISHMANIA_INFECTION", "− 1.00", "19", "STAT1 HLA-DRA HLA-DMA HLA-DPA1 HLA-DMB IL1B NCF4 TLR2 NCF2 ITGB2 TGFB1 FCGR3B FCGR2C FCGR2A PTGS2 C3"], ["INTESTINAL_IMMUNE_NETWORK_FOR_IGA_PRODUCTION", "− 0.99", "12", "HLA-DRA HLA-DMA HLA-DPA1 HLA-DMB CD40 TNFSF13B TGFB1 CD86 TNFRSF17 CXCR4"], ["PRIMARY_IMMUNODEFICIENCY", "− 1.43", "7", "PIK3R3 LYN RAC2 FCER1G BTK"]], "row_count": 21, "column_count": 4, "numeric_cells": 54, "header_rows": 1, "locator": "section[16]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:33686088:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b3820816732b16e4e36f157fdb7a2ca2cb437f4f966cebc637b56148ebbab0a2", "bytes": 791, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab3", "version": null, "note": "Active genes and their corresponding signal pathways they participate in after PPI analysis with PXR.", "structure": {"pmcid": "PMC7940411", "section_index": 17, "section_title": "Six genes were screened out that can interact and functionally associate with PXR", "row_count": 8, "column_count": 3}, "table": {"label": "Table 3", "caption": "Active genes and their corresponding signal pathways they participate in after PPI analysis with PXR.", "rows": [["Gene symbol", "Gene name", "Signal pathway"], ["PCK1", "phosphoenolpyruvate carboxykinase 1", "GLUCONEOGENESIS"], ["PPARGC1A", "PPARG Coactivator 1 Alpha", "INSULIN_PATHWAY"], ["CES2", "Carboxylesterase 2", "DRUG_METABOLISM_OTHER_ENZYMES"], ["ABCG2", "ATP Binding Cassette Subfamily G Member 2", "ABC_TRANSPORTERS"], ["CYP2B6", "Cytochrome P450 Family 2 Subfamily B Member 6", "METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450"], ["CXCL8", "C-X-C Motif Chemokine Ligand 8", "TOLL-LIKE_RECEPTOR_SIGNALING_PATHWAY"], ["CYTOKINE-CYTOKINE_RECEPTOR_INTERACTION", "", ""]], "row_count": 8, "column_count": 3, "numeric_cells": 7, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:33686088:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f64dcaae38d5dd03947e7057429fb0dd58369fe0034c655fabea0d749e885bef", "bytes": 481, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#Tab4", "version": null, "note": "Predicted sequences that PXR bind on the gene promoters listed below with the highest scores.", "structure": {"pmcid": "PMC7940411", "section_index": 18, "section_title": "The six genes were regulated by PXR", "row_count": 6, "column_count": 3}, "table": {"label": "Table 4", "caption": "Predicted sequences that PXR bind on the gene promoters listed below with the highest scores.", "rows": [["Gene symbol", "Score", "Predicted sequence"], ["CES2", "8.662", "AGGGACTCTGCGCCCTT"], ["ABCG2", "7.78554", "TTAAAACAATTGAACTC"], ["PCK1", "8.51", "GTGCCCCGGCCAACCTT"], ["PPARGC1A", "7.97", "TTAAACCCAATATACTT"], ["CYP2B6", "10.3884", 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