ArticleNeurogastroenterology and motility2020
Histone H3K9 methylation regulates chronic stress and IL-6-induced colon epithelial permeability and visceral pain.
Article in Neurogastroenterology and motility, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Histone modifications in biological age determination: mechanisms, biomarkers, and therapeutic perspectives.GeroScience · 2026Review
- G9a-mediated H3K9me2 orchestrates intestinal epithelial regeneration through epigenetic silencing of cell cycle-related genes.Nature communications · 2026Article
- Molecular Mechanisms of Human Pancreatic Islet Dysfunction Under Overnutrition Metabolic Stress.Diabetes · 2025Article
- Fine Particulate Matter (PM2.5) Disrupts Intestinal Barrier Function by Inducing Oxidative Stress and PI3K/AKT-Mediated Inflammation in Caco-2 Cells.International journal of molecular sciences · 2025Article
- Histone H3K9 Methylation Is Differentially Modified in Odontogenic Cyst and Tumors.European journal of dentistry · 2025Article
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Human colonic EVs induce murine enteric neuroplasticity via the lncRNA GAS5/miR-23/NMDA NR2B axis.JCI insight · 2025Article
- Review
- Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.International journal of molecular sciences · 2024Review
- Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.Molecular pain · 2024Article
- Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism.Expert opinion on drug metabolism & toxicology · 2024Review
- Plasma TNFRSF11B as a New Predictive Inflammatory Marker of Sepsis-ARDS with Endothelial Dysfunction.Journal of proteome research · 2023Article
- New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics.Journal of gastroenterology · 2023Review
- Review
- [Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
- Activation of goblet cell Piezo1 alleviates mucus barrier damage in mice exposed to WAS by inhibiting H3K9me3 modification.Cell & bioscience · 2023Article
- Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?Frontiers in immunology · 2023Review
- The dual role of interleukin-6 in Crohn's disease pathophysiology.Frontiers in immunology · 2023Review
- A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Negative elongation factor: a key factor in the maintenance of intestinal epithelial barrier integrity.Cellular & molecular immunology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundChronic stress is associated with activation of the HPA axis, elevation in pro-inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress-induced intestinal barrier dysfunction and visceral hyperalgesia.
methodsYoung adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco-2/BBE cells and human colonoids were treated with cortisol or IL-6 ± antagonists. Expression of TJ, IL-6, and H3K9 methylation status at gene promoters was measured. Transepithelial electrical resistance and FITC-dextran permeability were evaluated. KEY
resultsChronic stress induced IL-6 up-regulation prior to a decrease in TJ proteins in the rat colon. The IL-6 level inversely correlated with occludin expression. Treatment with IL-6 decreased occludin and induced visceral hyperalgesia. Chronic stress and IL-6 increased H3K9 methylation and decreased transcriptional GR binding to the occludin gene promoter, leading to down-regulation of protein expression and increase in paracellular permeability. Intrarectal administration of a H3K9 methylation antagonist prevented chronic stress-induced visceral hyperalgesia in the rat. In a human colonoid model, cortisol decreased occludin expression, which was prevented by the GR antagonist RU486, and IL-6 increased H3K9 methylation and decreased TJ protein levels, which were prevented by inhibitors of H3K9 methylation. CONCLUSIONS & INFERENCES: Our findings support a novel role for methylation of the repressive histone H3K9 to regulate chronic stress, pro-inflammatory cytokine-mediated reduction in colon TJ protein levels, and increase in paracellular permeability and visceral hyperalgesia.
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