ArticlePloS one2018
Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Protease-serpin-microbiome interactions in inflammatory bowel disease: toward integrated biomarkers of gut health.Gut microbes · 2026Review
- Development of a novel humanized gut-brain axis model as a tool toward personalized nutrition.Communications biology · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Biopsy samples from patients with irritable bowel syndrome, but not from those with mastocytosis or unspecific gastrointestinal complaints reveal unique nerve activation in all gut regions independent of mast cell density, histamine content or specific gastrointestinal symptoms.Frontiers in neuroscience · 2024Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Serpin-positive Bifidobacterium breve CNCM I-5644 improves intestinal permeability in two models of irritable bowel syndrome.Scientific reports · 2022Article
- Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS.Frontiers in physiology · 2022Review
- Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis.International journal of molecular sciences · 2021Article
- Gut Serpinome: Emerging Evidence in IBD.International journal of molecular sciences · 2021Review
- Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine.Journal of neurogastroenterology and motility · 2021Article
- Carbohydrate-controlled serine protease inhibitor (serpin) production in Bifidobacterium longum subsp. longum.Scientific reports · 2021Article
- The Possible Link Between Manufacturing and Probiotic Efficacy; a Molecular Point of View onFrontiers in microbiology · 2021Review
- Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk.iScience · 2020Article
- Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome.International journal of molecular sciences · 2020Review
- Enlightening the frontiers of neurogastroenterology through optogenetics.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Microbiota-neuroimmune cross talk in stress-induced visceral hypersensitivity of the bowel.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS.Gut · 2020Article
- UEG Week 2019 Poster Presentations.United European gastroenterology journal · 2019Article
- Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC).
methodEffects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis.
resultsNerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin-the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants.
conclusionProteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to characterise IBS.
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