Evidence map›Paper›PMID 29959891›Full record

ArticleBritish journal of pharmacology2018

Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism.

Morgane Sébert, Alexandre Denadai-Souza, Muriel Quaranta, Claire Racaud-Sultan, Sophie Chabot, Philippe Lluel, Nicolas Monjotin, Laurent Alric, Guillaume Portier, Sylvain Kirzin and 3 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Sexual dimorphism in PARBiology of sex differences · 2019
    Article
  11. Article
  12. Review
  13. Article
  14. Article
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

13 authors at 4 institutions in 2 countries.

Morgane SébertIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Alexandre Denadai-SouzaIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Muriel QuarantaIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Claire Racaud-SultanIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Sophie ChabotUROsphere, Ramonville, France.
Philippe LluelUROsphere, Ramonville, France.
Nicolas MonjotinInstitut de Recherche Pierre Fabre, Castres, France.
Laurent AlricDepartment of Internal Medicine and Digestive Diseases, CHU Purpan, Toulouse, France.
Guillaume PortierDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
Sylvain KirzinDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
Delphine BonnetIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Audrey FerrandIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Nathalie VergnolleIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.ORCID 0000-0003-1825-6015
Université Toulouse III - Paul Sabatier · FRUniversity of Calgary · CAHôpital Purpan · FRPierre Fabre (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeThrombin is massively released upon tissue damage associated with bleeding or chronic inflammation. The effects of this thrombin on tissue regrowth and repair has been scarcely addressed and only in cancer cell lines. Hence, the purpose of the present study was to determine thrombin's pharmacological effects on human intestinal epithelium growth, proliferation and apoptosis, using three-dimensional cultures of human colon organoids. EXPERIMENTAL APPROACH: Crypts were isolated from human colonic resections and cultured for 6 days, forming human colon organoids. Cultured organoids were exposed to 10 and 50 mU·mL KEY

resultsThrombin favoured organoid maturation leading to a decreased number of immature cystic structures and a concomitant increased number of larger structures releasing cell debris and apoptotic cells. The size of budding structures, metabolic activity and proliferation were significantly reduced in organoid cultures exposed to thrombin, while apoptosis was dramatically increased. Both PAR1 and PAR4 antagonists inhibited apoptosis regardless of thrombin doses. Thrombin-induced inhibition of proliferation and metabolic activity were reversed by PAR4 antagonist for thrombin's lowest dose and by PAR1 antagonist for thrombin's highest dose. CONCLUSIONS AND IMPLICATIONS: Overall, our data suggest that the presence of thrombin in the vicinity of human colon epithelial cells favours their maturation at the expense of their regenerative capacities. Our data point to thrombin and its two receptors PAR1 and PAR4 as potential molecular targets for epithelial repair therapies.

Indexed as

ApoptosisCell ProliferationCells, CulturedCell SurvivalColonHumansOrganoidsReceptor, PAR-1Receptors, ThrombinThrombinprotease-activated receptor 4Receptor, PAR-1Receptors, ThrombinThrombin

Identifiers

PMID29959891
PMCPMC6109216
OpenAlexW2811100276

What OpenQuestion holds

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LicenceCC BY-NC
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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.