ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05916274 (Pro-inflammatory Role of Extracellular DNA in Inflammatory Bowel Disease in Children), which is not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pro-inflammatory Role of Extracellular DNA in Inflammatory Bowel Disease in Children: Study of the cGAS-STING Pathway
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- cGAS/STING Signaling in Ulcerative Colitis: Mechanism and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Impact of BECLIN1 haploinsufficiency on goblet cell function and susceptibility to colitis.Cell death & disease · 2026Article
- Microbiota-derived butyrate inhibits colonic epithelial pyroptosis and mitigates DSS-induced colitis via interacting with aryl hydrocarbon receptor.Journal of translational medicine · 2026Article
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.Advanced biotechnology · 2026Review
- [Poricoic acid A alleviates dextran sulfate sodium-induced colitis in mice by regulating AMPK/mTOR-mediated autophagy and inhibiting intestinal epithelial cell apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The food grade bacterium Lactobacillus helveticus VEL12193 promotes autophagy by releasing membrane vesicles.Cell communication and signaling : CCS · 2026Article
- cGAS-STING and autophagy: crosstalk, molecular mechanisms, and targeted therapy.Archives of toxicology · 2026Review
- Autophagy Dysregulation in Crohn's Disease and Colorectal Cancer-An Analysis ofCurrent issues in molecular biology · 2025Article
- Exploring the anticancer potential of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides: synthesis, biological assessment, and computational analysis.BMC chemistry · 2025Article
- Autophagy: a double-edged sword in ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer.Frontiers in immunology · 2025Review
- cGAS-STING pathway as a promising target for digestive diseases: insights from natural plant products.Frontiers in nutrition · 2025Review
- BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.Autophagy reports · 2025Review
- PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation.Open life sciences · 2025Article
- The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases.Acta pharmacologica Sinica · 2024Review
- T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- YTHDC1 inhibits autophagy-dependent NF-κB signaling by stabilizing Beclin1 mRNA in macrophages.Journal of inflammation (London, England) · 2024Article
- The role of cGAS in epithelial dysregulation in inflammatory bowel disease and gastrointestinal malignancies.Frontiers in pharmacology · 2024Review
- cGAS-STING signaling pathway in intestinal homeostasis and diseases.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammatory bowel disease (IBD) represents a set of idiopathic and chronic inflammatory diseases of the gastrointestinal tract. Central to the pathogenesis of IBD is a dysregulation of normal intestinal epithelial homeostasis. cGAS is a DNA-sensing receptor demonstrated to promote autophagy, a mechanism that removes dysfunctional cellular components. Beclin-1 is a crucial protein involved in the initiation of autophagy. We hypothesized that cGAS plays a key role in intestinal homeostasis by upregulating Beclin-1-mediated autophagy. We evaluated intestinal cGAS levels in humans with IBD and in murine colonic tissue after performing a 2% dextran sulfate sodium (DSS) colitis model. Autophagy and cell death mechanisms were studied in cGAS KO and WT mice via qPCR, WB analysis, H&E, IF, and TUNEL staining. Autophagy was measured in stimulated intestinal epithelial cells (IECs) via WB analysis. Our data demonstrates cGAS to be upregulated during human and murine colitis. Furthermore, cGAS deficiency leads to worsened colitis and decreased levels of autophagy proteins including Beclin-1 and LC3-II. Co-IP demonstrates a direct binding between cGAS and Beclin-1 in IECs. Transfection of cGAS in stimulated HCT-116 cells leads to increased autophagy. IECs isolated from cGAS KO have diminished autophagic flux. cGAS KO mice subjected to DSS have increased cell death and cleaved caspase-3. Lastly, treatment of cGAS KO mice with rapamycin decreased the severity of colitis. Our data suggest that cGAS maintains intestinal epithelial homeostasis during human IBD and murine colitis by upregulating Beclin-1-mediated autophagy and preventing IEC death. Rescue of autophagy can attenuate the severity of colitis associated with cGAS deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.