Evidence map›Paper›PMID 17304351›Full record

ArticleThe Journal of clinical investigation2007

Role for protease activity in visceral pain in irritable bowel syndrome.

Nicolas Cenac, Christopher N Andrews, Marinella Holzhausen, Kevin Chapman, Graeme Cottrell, Patricia Andrade-Gordon, Martin Steinhoff, Giovanni Barbara, Paul Beck, Nigel W Bunnett and 4 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02952131 (Use of Autologous Adult Adipose-Derived Stem/Stromal Cells in Inflammatory Bowel Disease), which is not on this map. Cited by 237 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed, 4 pooled it
26.7field-weighted citation impact, top 1% 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.

NCT02952131 phase1 / phase2suspendednot on this mapstarted 2016, after this paper: background citation

Use of Autologous Adult Adipose-Derived Stem/Stromal Cells in Inflammatory Bowel Disease

TypeinterventionalSponsorHealeon Medical IncRan2016 to 2026Enrolled100ConditionsInflammatory Bowel DiseasesArmsLipoaspiration, AD-cSVF, Normal Saline IV
3 · Its place in the literature

Who cites it

237 citing papers in PubMed, 4 syntheses or guidelines pooled it, 578 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Article
  9. Article
  10. Review
  11. Review
  12. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  13. Article
  14. Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025
    Review
  20. The Duodenal Microenvironment in Functional Dyspepsia.Journal of neurogastroenterology and motility · 2025
    Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Nicolas CenacDepartment of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada.
Christopher N Andrews
Marinella Holzhausen
Kevin Chapman
Graeme Cottrell
Patricia Andrade-Gordon
Martin Steinhoff
Giovanni Barbara
Paul Beck
Nigel W Bunnett
Keith A Sharkey
Jose Geraldo P Ferraz
Eldon Shaffer
Nathalie Vergnolle
University of Calgary · CASpringhouse · USUniversity of Bologna · ITUniversity of California, San Francisco · USUniversity of Münster · DE

Funding

REGULATION OF SIGNALING BY CELL SURFACE PROTEOLYSISR01DK043207 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUNNETT, NIGEL W · 1993 to 2011
$1.7M
REGULATION OF SIGNALING BY CELL-SURFACE PROTEOLYSISR56DK043207 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUNNETT, NIGEL W · 2010 to 2010
$348k
NIDDK NIH HHS DK43207NIDDK NIH HHS DK57480NIDDK NIH HHS R01 DK043207NIDDK NIH HHS R56 DK043207
6 · The paper itself

Abstract

Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-kappaB. In addition, increased proteolytic activity was measured in vivo, in colonic washes from IBS compared with control patients. Trypsin and tryptase expression and release were increased in colonic biopsies from IBS patients compared with control subjects. Biopsies from IBS patients (but not controls) released mediators that sensitized murine sensory neurons in culture. Sensitization was prevented by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR2). Supernatants from colonic biopsies of IBS patients, but not controls, also caused somatic and visceral hyperalgesia and allodynia in mice, when administered into the colon. These pronociceptive effects were inhibited by serine protease inhibitors and a PAR2 antagonist and were absent in PAR2-deficient mice. Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR2.

Indexed as

Abdominal PainAdultalpha 1-AntitrypsinColonEndopeptidasesFemaleHumansHyperalgesiaIrritable Bowel SyndromeMaleMiddle AgedNeurons, AfferentNF-kappa BReceptor, PAR-2Serine Proteinase InhibitorsTrypsinalpha 1-AntitrypsinEndopeptidasesNF-kappa BReceptor, PAR-2Serine Proteinase InhibitorsSERPINA1 protein, humanTrypsinTryptases

Identifiers

PMID17304351
PMCPMC1794118
OpenAlexW2140528350

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.