Evidence map›Paper›PMID 27492333›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016

The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction.

Natalie J Ronaghan, Judie Shang, Vadim Iablokov, Raza Zaheer, Pina Colarusso, Sébastien Dion, Antoine Désilets, Richard Leduc, Jerrold R Turner, Wallace K MacNaughton

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  2. Article
  3. International journal of molecular sciences · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Mulberroside A from Cortex Mori Enhanced Gut Integrity in Diabetes.Evidence-based complementary and alternative medicine : eCAM · 2021
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Gut pathogens · 2019
    Article
  16. Article
  17. Review
  18. Cellular Tight Junctions Prevent EffectiveFrontiers in cellular and infection microbiology · 2018
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Natalie J RonaghanDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Judie ShangDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Vadim IablokovDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Raza ZaheerDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Pina ColarussoDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Sébastien DionDépartement de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Antoine DésiletsDépartement de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Richard LeducDépartement de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Jerrold R TurnerDepartments of Pathology and Medicine (GI), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Wallace K MacNaughtonDepartment of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and wmacnaug@ucalgary.ca.
University of Calgary · CAUniversité de Sherbrooke · CABrigham and Women's Hospital · US

Funding

ZO-1-MEDIATED PROTEIN INTERACTIONS: REGULATORS AND INTEGRATORS OF DIVERSE EPITHELIAL FUNCTIONS IN HEALTH AND DISEASER01DK061931 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2001 to 2026
$15.0M
Therapeutic targeting of protein interactions to reverse MLCK1-mediated intestinal barrier loss and ameliorate disease.R01DK068271 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2005 to 2026
$11.3M
CIHR MOP-119490NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271
6 · The paper itself

Abstract

Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Understanding how the tight junction is modified to maintain barrier function may provide avenues for treatment of IBD. We have previously shown that the apical addition of serine proteases to intestinal epithelial cell lines causes a rapid and sustained increase in transepithelial electrical resistance (TER), but the mechanisms are unknown. We hypothesized that serine proteases increase barrier function through trafficking and insertion of tight junction proteins into the membrane, and this could enhance recovery of a disrupted monolayer after calcium switch or cytokine treatment. In the canine epithelial cell line, SCBN, we showed that matriptase, an endogenous serine protease, could potently increase TER. Using detergent solubility-based cell fractionation, we found that neither trypsin nor matriptase treatment changed levels of tight junction proteins at the membrane. In a fast calcium switch assay, serine proteases did not enhance the rate of recovery of the junction. In addition, serine proteases could not reverse barrier disruption induced by IFNγ and TNFα. We knocked down occludin in our cells using siRNA and found this prevented the serine protease-induced increase in TER. Using fluorescence recovery after photobleaching (FRAP), we found serine proteases induce a greater mobile fraction of occludin in the membrane. These data suggest that a functional tight junction is needed for serine proteases to have an effect on TER, and that occludin is a crucial tight junction protein in this mechanism.

Indexed as

AnimalsCell LineDogsElectric ImpedanceElectrophysiological PhenomenaEpithelial CellsIntestinal MucosaOccludinProtein TransportSerine EndopeptidasesSerine ProteasesTight Junction ProteinsTight JunctionsTrypsinmatriptaseOccludinSerine EndopeptidasesSerine ProteasesTight Junction ProteinsTrypsinbarrier functioninflammationproteasestight junction

Identifiers

PMID27492333
PMCPMC5076006
OpenAlexW2487525155

What OpenQuestion holds

Textmetadata
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.