Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells
Abstract
:1. Introduction
2. Results
2.1. Summary of Transcriptome Sequencing Data
2.2. Analysis of Differentially Expressed Genes in Caco-2 Cells Stimulated with CotG-p75
2.3. Gene Ontology Enrichment Analysis
2.4. KEGG Pathway Enrichment Analysis
2.5. RNA-Seq Data Validation by RT-qPCR
2.6. Effects of CotG-p75 on HBEGF and CCL20 Protein Expression
2.7. Comparison of Transcriptional Responses of HT-29 and Caco-2 Cells Stimulated by CotG-p75
3. Discussion
4. Materials and Methods
4.1. Spore Preparation
4.2. Cell Culture and Treatments
4.3. Cell Viability Assay
4.4. Total RNA Isolation, cDNA Library Construction, and RNA-Sequencing
4.5. Analysis of Differentially Expressed Genes (DEGs)
4.6. Functional Analyses of DEGs
4.7. Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR) Confirmation
4.8. Heparin Binding-Epidermal Growth Factor (HBEGF) and CC Motif Chemokine Ligand (CCL20) Protein Expression
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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GO ID | GO Description | Adjusted p-Value a | Cluster Frequency b | Total Frequency c |
---|---|---|---|---|
Biological process | ||||
0042221 | response to chemical stimulus | 3.70 × 10−15 | 54/202 (26.7%) | 1466/17,784 (8.2%) |
0042330 | taxis | 5.20 × 10−15 | 20/202 (9.9%) | 169/17,784 (0.9%) |
0006935 | chemotaxis | 5.20 × 10−15 | 20/202 (9.9%) | 169/17,784 (0.9%) |
0006952 | defense response | 6.97 × 10−13 | 32/202 (15.8%) | 621/17,784 (3.4%) |
0009605 | response to external stimulus | 1.03 × 10−12 | 30/202 (14.8%) | 552/17,784 (3.1%) |
0048518 | positive regulation of biological process | 1.43 × 10−12 | 63/202 (31.1%) | 2210/17,784 (12.4%) |
0009611 | response to wounding | 3.92 × 10−12 | 29/202 (14.3%) | 543/17,784 (3.0%) |
0048522 | positive regulation of cellular process | 8.84 × 10−12 | 58/202 (28.7%) | 2006/17,784 (11.2%) |
0002376 | immune system process | 3.68 × 10−11 | 37/202 (18.3%) | 949/17,784 (5.3%) |
0007626 | locomotory behavior | 4.31 × 10−11 | 20/202 (9.9%) | 273/17,784 (1.5%) |
0048513 | organ development | 1.33 × 10−10 | 52/202 (25.7%) | 1792/17,784 (10.0%) |
0023046 | signaling process | 1.63 × 10−10 | 58/202 (28.7%) | 2157/17,784 (12.1%) |
0023060 | signal transmission | 1.63 × 10−10 | 58/202 (28.7%) | 2157/17,784 (12.1%) |
0048731 | system development | 2.26 × 10−10 | 62/202 (30.6%) | 2422/17,784 (13.6%) |
0051239 | regulation of multicellular organismal process | 2.71 × 10−10 | 38/202 (18.8%) | 1068/17,784 (6.0%) |
0032502 | developmental process | 3.55 × 10−10 | 74/202 (36.6%) | 3234/17,784 (18.1%) |
0007275 | multicellular organismal development | 3.84 × 10−10 | 70/202 (34.6%) | 2971/17,784 (16.7%) |
0048856 | anatomical structure development | 4.62 × 10−10 | 65/202 (32.1%) | 2656/17,784 (14.9%) |
0065007 | biological regulation | 5.60 × 10−10 | 122/202 (60.3%) | 6941/17,784 (39.0%) |
0006954 | inflammatory response | 5.80 × 10−10 | 20/202 (9.9%) | 316/17,784 (1.7%) |
Molecular function | ||||
0008009 | chemokine activity | 2.47 × 10−9 | 9/202 (4.4%) | 47/17,784 (0.2%) |
0042379 | chemokine receptor binding | 6.35 × 10−9 | 9/202 (4.4%) | 52/17,784 (0.2%) |
0001664 | G-protein-coupled receptor binding | 4.92 × 10−8 | 12/202 (5.9%) | 136/17,784 (0.7%) |
0005102 | receptor binding | 5.53 × 10−8 | 31/202 (15.3%) | 922/17,784 (5.1%) |
0005126 | cytokine receptor binding | 2.13 × 10−7 | 13/202 (6.4%) | 186/17,784 (1.0%) |
0005125 | cytokine activity | 4.12 × 10−7 | 13/202 (6.4%) | 197/17,784 (1.1%) |
Cellular component | ||||
0005615 | extracellular space | 1.91 × 10−11 | 33/202 (16.3%) | 747/17,784 (4.2%) |
0044421 | extracellular region part | 1.00 × 10−10 | 37/202 (18.3%) | 983/17,784 (5.5%) |
0005576 | extracellular region | 1.91 × 10−7 | 49/202 (24.2%) | 2025/17,784 11.3% |
Pathway ID | KEGG Pathway | Counts | Adjusted p-Val. a | Genes |
---|---|---|---|---|
has04668 | TNF signaling pathway | 15 | 7.13 × 10−13 | CSF1, FOS, CXCL1, CXCL2, CXCL3, BIRC3, ICAM1, IL1B, CXCL10, IRF1, NFKBIA, BCL3, CCL20, CX3CL1, TNFAIP3 |
has04657 | IL-17 signaling pathway | 13 | 2.95 × 10−11 | FOS, CXCL1, CXCL2, CXCL3, IL1B, CXCL8, CXCL10, LCN2, NFKBIA, CCL20, TNFAIP3, FOSL1, IKBKE |
has04064 | NF-κB signaling pathway | 13 | 5.90 × 10−11 | CXCL1, CXCL2, CXCL3, BIRC3, ICAM1, IL1B, CXCL8, NFKB2, NFKBIA, PLAU, RELB, TNFAIP3, TNFRSF11A |
has04062 | Chemokine signaling pathway | 14 | 2.50 × 10−9 | VAV3, CCR6, GNAI1, CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, NFKBIA, CCL20, CCL22, CXCL11, CX3CL1, SOS1 |
has05323 | Rheumatoid arthritis | 11 | 5.90 × 10−9 | CSF1, FOS, 245972, CXCL1, CXCL2, CXCL3, ICAM1, IL1B, CXCL8, CCL20, TNFRSF11A |
has04061 | Viral protein interaction with cytokine and cytokine receptor | 11 | 9.49 × 10−9 | CCR6, CSF1, CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, CCL20, CCL22, CXCL11, CX3CL1 |
has04625 | C-type lectin receptor signaling pathway | 11 | 1.16 × 10−8 | EGR2, MRAS, IL1B, IRF1, ITPR1, NFKB2, NFKBIA, RELB, BCL3, CX3CL1, IKBKE |
has05417 | Lipid and atherosclerosis | 13 | 5.84 × 10−8 | 10451, CYP1A1, FOS, CXCL1, CXCL2, CXCL3, ICAM1, IL1B, CXCL8, LAMA4, NFKBIA, OLR1, IKBKE |
has05200 | Pathways in cancer | 18 | 7.05 × 10−8 | ETS1, FGF9, FOS, RASGRP3, GNAI1, BIRC3, CXCL8, LAMA4, NFKB2, NFKBIA, NOS2, WNT4, SOS1, STAT5A, TGFA, WNT5A, WNT6, WNT7B |
has04010 | MAPK signaling pathway | 14 | 1.33 × 10−7 | CSF1, DUSP4, DUSP6, FGF9, MRAS, FOS, RASGRP3, IL1B, AREG, MEF2C, NFKB2, RELB, SOS1, TGFA |
Gene Symbol | Gene Name | Fold Change | Raw p-Value |
---|---|---|---|
CXCL10 | C-X-C motif chemokine ligand 10 | 35.58 | 5.23 × 10−34 |
CCL20 | C-C motif chemokine ligand 20 | 21.17 | 0.00 |
CXCL8 | C-X-C motif chemokine ligand 8 | 20.17 | 4.15 × 10−38 |
CXCL1 | C-X-C motif chemokine ligand 1 | 16.81 | 9.56 × 10−41 |
BIRC3 | baculoviral IAP repeat containing 3 | 11.90 | 3.76 × 10−218 |
CXCL3 | C-X-C motif chemokine ligand 3 | 8.10 | 3.93 × 10−52 |
CXCL11 | C-X-C motif chemokine ligand 11 | 5.91 | 2.38 × 10−3 |
CXCL2 | C-X-C motif chemokine ligand 2 | 5.59 | 6.66 × 10−41 |
CX3CL1 | C-X3-C motif chemokine ligand 1 | 5.54 | 9.45 × 10−9 |
PLAU | plasminogen activator, urokinase | 5.36 | 8.88 × 10−22 |
TNFRSF11A | TNF receptor superfamily member 11a | 4.98 | 3.77 × 10−7 |
CSF1 | colony stimulating factor 1 | 4.92 | 1.23 × 10−25 |
TNFAIP3 | TNF α induced protein 3 | 3.44 | 7.71 × 10−119 |
IL1B | interleukin 1 β | 3.38 | 2.07 × 10−4 |
RELB | RELB proto-oncogene, NF-κB subunit | 2.83 | 1.63 × 10−35 |
NFKBIA | NF-κB inhibitor α | 2.80 | 1.67 × 10−75 |
SOS1 | SOS Ras/Rac guanine nucleotide exchange factor 1 | 2.75 | 7.76 × 10−57 |
IKBKE | inhibitor of nuclear factor κB kinase subunit epsilon | 2.67 | 5.34 × 10−33 |
CCL22 | C-C motif chemokine ligand 22 | 2.57 | 4.78 × 10−2 |
LCN2 | lipocalin 2 | 2.50 | 2.14 × 10−2 |
FOS | Fos proto-oncogene, AP-1 transcription factor subunit | 2.36 | 6.24 × 10−23 |
FOSL1 | FOS like 1, AP-1 transcription factor subunit | 2.34 | 4.92 × 10−11 |
ICAM1 | intercellular adhesion molecule 1 | 2.24 | 9.38 × 10−43 |
BCL3 | B-cell CLL/lymphoma 3 | 2.19 | 6.45 × 10−35 |
CCR6 | C-C motif chemokine receptor 6 | 2.13 | 3.81 × 10−4 |
IRF1 | interferon regulatory factor 1 | 2.11 | 7.13 × 10−26 |
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Kang, S.-J.; Jun, J.-S.; Hong, K.-W. Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells. Int. J. Mol. Sci. 2022, 23, 14519. https://doi.org/10.3390/ijms232314519
Kang S-J, Jun J-S, Hong K-W. Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells. International Journal of Molecular Sciences. 2022; 23(23):14519. https://doi.org/10.3390/ijms232314519
Chicago/Turabian StyleKang, Soo-Ji, Ji-Su Jun, and Kwang-Won Hong. 2022. "Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells" International Journal of Molecular Sciences 23, no. 23: 14519. https://doi.org/10.3390/ijms232314519
APA StyleKang, S.-J., Jun, J.-S., & Hong, K.-W. (2022). Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells. International Journal of Molecular Sciences, 23(23), 14519. https://doi.org/10.3390/ijms232314519