ArticleGastroenterology2020
Activating Transcription Factor 6 Mediates Inflammatory Signals in Intestinal Epithelial Cells Upon Endoplasmic Reticulum Stress.
Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effect of mindfulness interventions on stress in medical students: A systematic review and meta-analysis.PloS one · 2023Pooled it
- Dysregulation of miR-140-3p is involved in the pathogenesis of pulpitis via the regulation of ACSL1.Odontology · 2026Article
- Treatment with saponins fromNutrition research and practice · 2026Article
- Endoplasmic Reticulum Stress-Induced Endothelial Cell Pyroptosis Contributes to Pulmonary Vascular Remodeling and Pulmonary Arterial Hypertension via IRE1α/Caspase-3/GSDME Pathway.Journal of the American Heart Association · 2026Article
- Role of miRNAs from mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice.Neural regeneration research · 2026Article
- Tunicamycin-induced ER stress promotes inflammation in SH-SY5Y cells through ROS-NF-κB-SIRT1 pathway.Molecular biology reports · 2026Article
- Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.Advanced biotechnology · 2026Review
- Macrophages signal cross-talks under hyperglycemic conditions and their link to cyclophilins.Molecular medicine (Cambridge, Mass.) · 2026Article
- Integrated Phosphoproteomics Identifies TGFβ-Dependent Phosphorylation Events Linking Kinase Signaling to Autophagy in Palatogenesis.Proteomes · 2026Article
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- Activating transcription factor 6 is involved in the beneficial effects of growth hormone-releasing hormone antagonists in the corneal endothelium.Frontiers in ophthalmology · 2026Article
- Endoplasmic reticulum stress and oxidative imbalance is the missing link in fibromyalgia pathophysiology.Scientific reports · 2025Article
- Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies.npj metabolic health and disease · 2025Review
- The effect of oleoylethanolamide supplementation on cardiometabolic factors: a systematic review and meta-analysis.Cardiovascular endocrinology & metabolism · 2025Review
- Auxilin in enterocytes controls intestinal homeostasis through inter-cell communication.Cell death & disease · 2025Article
- Activated TBK1 promotes ACSL1-mediated microglia lipid droplet accumulation and neuroinflammation in Parkinson's disease.Journal of neuroinflammation · 2025Article
- Endoplasmic reticulum stress: an emerging therapeutic target for preeclampsia†.Biology of reproduction · 2025Review
- Susceptibility to inflammatory bowel diseases promotes invasive carcinomas in a murine model of ATF6-driven colon cancer.Journal of Crohn's & colitis · 2025Article
- ZnO@Cu5.4O Nanoparticle Alleviates Inflammatory Responses of Intestinal Epithelial Cells by Inhibiting the Expression of GSDMB.ACS omega · 2025Article
- Dissecting the METTL3/STC2 axis in colorectal cancer: implications for drug resistance and metastasis.Cell biology and toxicology · 2025Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Funding
Abstract
BACKGROUND &
aimsExcess and unresolved endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) promotes intestinal inflammation. Activating transcription factor 6 (ATF6) is one of the signaling mediators of ER stress. We studied the pathways that regulate ATF6 and its role for inflammation in IECs.
methodsWe performed an RNA interference screen, using 23,349 unique small interfering RNAs targeting 7783 genes and a luciferase reporter controlled by an ATF6-dependent ERSE (ER stress-response element) promoter, to identify proteins that activate or inhibit the ATF6 signaling pathway in HEK293 cells. To validate the screening results, intestinal epithelial cell lines (Caco-2 cells) were transfected with small interfering RNAs or with a plasmid overexpressing a constitutively active form of ATF6. Caco-2 cells with a CRISPR-mediated disruption of autophagy related 16 like 1 gene (ATG16L1) were used to study the effect of ATF6 on ER stress in autophagy-deficient cells. We also studied intestinal organoids derived from mice that overexpress constitutively active ATF6, from mice with deletion of the autophagy related 16 like 1 or X-Box binding protein 1 gene in IECs (Atg16l1
resultsWe identified and validated 15 suppressors and 7 activators of the ATF6 signaling pathway; activators included the regulatory subunit of casein kinase 2 (CSNK2B) and acyl-CoA synthetase long chain family member 1 (ACSL1). Knockdown or chemical inhibition of CSNK2B and ACSL1 in Caco-2 cells reduced activity of the ATF6-dependent ERSE reporter gene, diminished transcription of the ATF6 target genes HSP90B1 and HSPA5 and reduced NF-κB reporter gene activation on tunicamycin stimulation. Atg16l1
conclusionsIleal IECs from patients with CD have higher levels of activated ATF6, which is regulated by CSNK2B and HSPA5. ATF6 increases expression of TNF and other inflammatory cytokines in response to ER stress in these cells and in organoids from Atg16l1
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