Chronic Psychological Stress Alters Gene Expression in Rat Colon Epithelial Cells Promoting Chromatin Remodeling, Barrier Dysfunction and Inflammation
Open accessAbstract
Chronic stress is commonly associated with enhanced abdominal pain (visceral hypersensitivity), but the cellular mechanisms underlying how chronic stress induces visceral hypersensitivity are poorly understood. In this study, we examined changes in gene expression in colon epithelial cells from a rat model using RNA-sequencing to examine stress-induced changes to the transcriptome. Following chronic stress, the most significantly up-regulated genes included Atg16l1, Coq10b, Dcaf13, Nat2, Ptbp2, Rras2, Spink4 and down-regulated genes including Abat, Cited2, Cnnm2, Dab2ip, Plekhm1, Scd2, and Tab2. The primary altered biological processes revealed by network enrichment analysis were inflammation/immune response, tissue morphogenesis and development, and nucleosome/chromatin assembly. The most significantly down-regulated process was the digestive system development/function, whereas the most significantly up-regulated processes were inflammatory response, organismal injury, and chromatin remodeling mediated by H3K9 methylation. Furthermore, a subpopulation of stressed rats demonstrated very significantly altered gene expression and transcript isoforms, enriched for the differential expression of genes involved in the inflammatory response, including upregulation of cytokine and chemokine receptor gene expression coupled with downregulation of epithelial adherens and tight junction mRNAs. In summary, these findings support that chronic stress is associated with increased levels of cytokines and chemokines, their downstream signaling pathways coupled to dysregulation of intestinal cell development and function. Epigenetic regulation of chromatin remodeling likely plays a prominent role in this process. Results also suggest that super enhancers play a primary role in chronic stress-associated intestinal barrier dysfunction.
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There is a genetic predisposition to stress-induced immune dysregulation.
“This indicates a genetic predisposition to stress-induced immune dysregulation [13,27,62].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [13]
Chronic stress is linked with higher levels of Th1 cells in individuals carrying specific minor alleles of the glucocorticoid receptor and interferon-gamma receptor genes.
“The results showed that chronic stress is linked with higher levels of Th1 cells in individuals carrying specific minor alleles of the glucocorticoid receptor and interferon-gamma receptor genes.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [13]
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Higgins, G. A., Georgoff, P. E., Nikolian, V. C., Allyn-Feuer, A., Pauls, B., Higgins, R., Athey, B. D., & Alam, H. E. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2130-6 · Cited by 28 · see citing works
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The Serum Levels of CCL2 and CCL16 Expression in Patients with Irritable Bowel Syndrome.
Hayatbakhsh, M. M., Shabgah, A. G., Pishgouyi, S., Afshari, J. T., Zeidabadi, H., & Mohammadi, M. (2019) · Europe PMC (PubMed Central) · Cited by 12 · see citing works
Overexpression of let‐7d explains down‐regulated KDM3A and ENO2 in the pathogenesis of preeclampsia
Xu, Q., Song, Y., & Lu, L. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16299 · Cited by 9 · see citing works
Flagged first, then by citations
1 of the 98 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Intestinal Barrier Impairment, Preservation, and Repair: An Update
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Nutrigenomics and Precision Nutrition in Inflammatory Bowel Disease
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- Authors
- Wiley, J. W., Higgins, G. A., & Hong, S.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Hong, Shuangsong
- Venue
- PeerJ
- Publisher
- PeerJ
- Published
- 2022-04-29
- Volume
- 10
- Pages
- e13287
- ISSN
- 2167-8359 (ISSN-L)
- PMC
- PMC9059753
- OpenAlex
- W4225123060
- Cited by
- 21
- References
- 98
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 8 · 2023: 2 · 2022: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PeerJ (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01DK098205, R21AT009253, R21NS113127)
- The University of Michigan Center for Gastrointestinal Research (P30 DK34933)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- chronic psychological stress, visceral hypersensitivity, colonic epithelial cells, transcriptome, chromatin remodeling, H3K9 methylation, intestinal barrier dysfunction, tight junctions, adherens junctions, intestinal inflammation, cytokines and chemokines, super-enhancers, epigenetic regulation, intestinal development
- MeSH terms
- Animals, Colon, Epithelial Cells, Gastrointestinal Diseases, Hyperalgesia, Inflammation, Stress, Psychological, Gene Expression, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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