Evidence map›Paper›PMID 28096305›Full record

ArticleGut2017

Epithelial expression and function of trypsin-3 in irritable bowel syndrome.

Claire Rolland-Fourcade, Alexandre Denadai-Souza, Carla Cirillo, Cintya Lopez, Josue Obed Jaramillo, Cleo Desormeaux, Nicolas Cenac, Jean-Paul Motta, Muriel Larauche, Yvette Taché and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Current research in microbial sciences · 2026
    Article
  4. Review
  5. Article
  6. Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025
    Review
  11. 5-HTThe Journal of physiology · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Identification of a secreted protease frombioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 8 institutions in 4 countries.

Claire Rolland-FourcadeIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Alexandre Denadai-SouzaIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Carla CirilloLaboratory for Enteric Neuroscience (LENS), TARGID, University of Leuven, Leuven, Belgium.
Cintya LopezGastrointestinal Diseases Research Unit, , General Hospital, Queen's University School of Medicine, Kingston, Ontario, Canada.
Josue Obed JaramilloGastrointestinal Diseases Research Unit, , General Hospital, Queen's University School of Medicine, Kingston, Ontario, Canada.
Cleo DesormeauxIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Nicolas CenacIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Jean-Paul MottaIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Muriel LaraucheOppenheimer Family Center for Neurobiology of Stress and Resilience and CURE: Digestive Diseases Research Center, Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Yvette TachéOppenheimer Family Center for Neurobiology of Stress and Resilience and CURE: Digestive Diseases Research Center, Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Pieter Vanden BergheLaboratory for Enteric Neuroscience (LENS), TARGID, University of Leuven, Leuven, Belgium.
Michel NeunlistInserm, UMR913, Nantes, France.
Emmanuel CoronInserm, UMR913, Nantes, France.
Sylvain KirzinDepartment of Internal Medicine and Digestive Diseases, Pole Digestif, CHU Toulouse, Toulouse, France.
Guillaume PortierDepartment of Internal Medicine and Digestive Diseases, Pole Digestif, CHU Toulouse, Toulouse, France.
Delphine BonnetDepartment of Internal Medicine and Digestive Diseases, Pole Digestif, CHU Toulouse, Toulouse, France.
Laurent AlricDepartment of Internal Medicine and Digestive Diseases, Pole Digestif, CHU Toulouse, Toulouse, France.
Stephen VannerGastrointestinal Diseases Research Unit, , General Hospital, Queen's University School of Medicine, Kingston, Ontario, Canada.
Celine DeraisonIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Nathalie VergnolleIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Digestive Health Research Institute · FRÉcole Nationale Vétérinaire de Toulouse · FRInserm · FRQueen's University · CACenter for Digestive and Liver Diseases · USKU Leuven · BENantes Université · FRUniversité Toulouse III - Paul Sabatier · FR

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Women's Health and Functional Visceral Disorders CenterP50DK064539 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYER, EMERAN A · 2002 to 2017
$17.5M
Stress-Induced Activition of Colonic Motor FunctionR01DK057238 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TACHE, YVETTE FRANCE · 2000 to 2015
$3.3M
Modulation of Colonic Epithelial Permeability by Sex HormonesK01DK088937 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LARAUCHE, MURIEL · 2011 to 2015
$647k
NIDDK NIH HHS K01 DK088937NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P50 DK064539NIDDK NIH HHS R01 DK057238
6 · The paper itself

Abstract

objectivesProteases are key mediators of pain and altered enteric neuronal signalling, although the types and sources of these important intestinal mediators are unknown. We hypothesised that intestinal epithelium is a major source of trypsin-like activity in patients with IBS and this activity signals to primary afferent and enteric nerves and induces visceral hypersensitivity.

designTrypsin-like activity was determined in tissues from patients with IBS and in supernatants of Caco-2 cells stimulated or not. These supernatants were also applied to cultures of primary afferents. mRNA isoforms of trypsin (

resultsWe showed that stimulated intestinal epithelial cells released trypsin-like activity specifically from the basolateral side. This activity was able to activate sensory neurons. In colons of patients with IBS, increased trypsin-like activity was associated with the epithelium. We identified that trypsin-3 was the only form of trypsin upregulated in stimulated intestinal epithelial cells and in tissues from patients with IBS. Trypsin-3 was able to signal to human submucosal enteric neurons and mouse sensory neurons, and to induce visceral hypersensitivity in vivo, all by a protease-activated receptor-2-dependent mechanism.

conclusionsIn IBS, the intestinal epithelium produces and releases the active protease trypsin-3, which is able to signal to enteric neurons and to induce visceral hypersensitivity.

Indexed as

AnimalsCaco-2 CellsCase-Control StudiesColonCulture Media, ConditionedDipeptidesEnteric Nervous SystemEpithelial CellsFemaleGanglia, SpinalHumansHypersensitivityIntestinal MucosaIrritable Bowel SyndromeIsoxazolesLipopolysaccharides5-isoxazoyl-cyclohexylalanyl-isoleucyl-spiroindane-1,4'-piperidineCulture Media, ConditionedDipeptidesIsoxazolesLipopolysaccharidesPRSS1 protein, humanPRSS2 protein, humanPRSS3 protein, humanPRSS3 protein, mouseReceptor, PAR-2RNA, MessengerTrypsinTrypsinogenABDOMINAL PAINIRRITABLE BOWEL SYNDROMENERVE - GUT INTERACTIONSTRYPSIN

Identifiers

PMID28096305
PMCPMC5595105
OpenAlexW2574980908

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.