ArticleEMBO molecular medicine2021
A novel P2X2-dependent purinergic mechanism of enteric gliosis in intestinal inflammation.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 79 citations in OpenAlex.
- P2X7R+CD8αβiScience · 2026Article
- The role of NLRP3 inflammasome in the development of postoperative ileus and its molecular mechanism in male mice.Physiological reports · 2026Article
- Short-chain fatty acids mitigate inflammation and associated metabolic programming of human stem cell-derived enteric glial cells.Journal of neuroinflammation · 2026Article
- Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.Purinergic signalling · 2026Review
- STING controls glycolysis and histone lactylation to drive macrophage metabolic reprogramming in postoperative ileus.Communications biology · 2026Article
- Purinergic signaling in the gut neuro-glial-immune axis: mechanisms of homeostasis, inflammation, and gastrointestinal dysfunction.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Generalised Hodgkin-Huxley model captures human P2X and AMPA receptor currents.The Journal of physiology · 2026Article
- Glial Connexin-43 Is a Pathogenic Mechanism Promoting Gut Inflammation in Postoperative Ileus Induced by Gut Surgical Manipulation With Potential Relevance to Humans.Cellular and molecular gastroenterology and hepatology · 2026Article
- Ungluing the Mystery of Postoperative Ileus: Enteric Glial Connexin 43 Promotes the Development of Inflammation.Cellular and molecular gastroenterology and hepatology · 2026Article
- Enteric glia and purinergic signaling in health and disease.Neuropharmacology · 2025Review
- Clinicopathological characterization of enteric glia in colorectal cancer: Insights from a population-based cohort.Journal of neuropathology and experimental neurology · 2025Article
- P2 receptors signaling in the esophagus: from inflammation to cancer.Purinergic signalling · 2025Review
- Subtype-specific structural features of the hearing loss-associated human P2X2 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- P2 purinergic receptors regulate the progression of colorectal cancer.Purinergic signalling · 2025Review
- Use of Human In Vitro Gut Specimens for Translational Neurogastroenterology and Motility in the 21st Century.Neurogastroenterology and motility · 2025Review
- The role of reactive enteric glia-macrophage interactions in acute and chronic inflammation.Neurogastroenterology and motility · 2025Review
- The functional role of P2 purinergic receptors in the progression of gastric cancer.Purinergic signalling · 2025Review
- Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis.iScience · 2025Article
- Intestinal neuron-associated macrophages in health and disease.Nature immunology · 2025Review
- Layer-specific molecular signatures of colon anastomotic healing and leakage in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 3 countries.
Funding
Abstract
Enteric glial cells (EGC) modulate motility, maintain gut homeostasis, and contribute to neuroinflammation in intestinal diseases and motility disorders. Damage induces a reactive glial phenotype known as "gliosis", but the molecular identity of the inducing mechanism and triggers of "enteric gliosis" are poorly understood. We tested the hypothesis that surgical trauma during intestinal surgery triggers ATP release that drives enteric gliosis and inflammation leading to impaired motility in postoperative ileus (POI). ATP activation of a p38-dependent MAPK pathway triggers cytokine release and a gliosis phenotype in murine (and human) EGCs. Receptor antagonism and genetic depletion studies revealed P2X2 as the relevant ATP receptor and pharmacological screenings identified ambroxol as a novel P2X2 antagonist. Ambroxol prevented ATP-induced enteric gliosis, inflammation, and protected against dysmotility, while abrogating enteric gliosis in human intestine exposed to surgical trauma. We identified a novel pathogenic P2X2-dependent pathway of ATP-induced enteric gliosis, inflammation and dysmotility in humans and mice. Interventions that block enteric glial P2X2 receptors during trauma may represent a novel therapy in treating POI and immune-driven intestinal motility disorders.
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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 Socratic graph.