Related Experiment Video

Updated: Jul 30, 2025

Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
10:30

Visualization of IL-22-expressing Lymphocytes Using Reporter Mice

Published on: January 25, 2017

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IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling

Tom Breugelmans1,2, Wout Arras1,2, Baptiste Oosterlinck1,2

  • 1Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.

Cells
|May 13, 2023
PubMed

Insights

Aberrant MUC13 signaling, often seen in inflammatory bowel diseases (IBD), disrupts intestinal barrier function. MUC13 plays a dual role in colitis, with MUC1 acting as a collaborator in barrier dysfunction.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • Overexpression of transmembrane mucin MUC13 is observed in inflammatory bowel diseases (IBD).
  • MUC13 overexpression may impact epithelial barrier function, a critical factor in IBD pathogenesis.
  • The role of MUC13 in inflammation-induced intestinal barrier disruption requires further elucidation, particularly its interaction with MUC1.

Purpose of the Study:

  • To investigate how inflammation-induced MUC13 disrupts epithelial barrier integrity in IBD.
  • To explore the signaling pathways involved in MUC13-mediated barrier dysfunction.
  • To determine the role of MUC1 in this process and its expression in IBD patients.

Main Methods:

  • RNA sequencing and permeability assays in MUC1/MUC13 siRNA-transfected cells stimulated with IL-22.
  • In vivo studies using DSS-induced colitis models in wildtype and Muc13 knockout mice.
  • Analysis of MUC13, its regulators, and barrier mediators in IBD patient samples.

Main Results:

  • Mucin knockdown affected barrier mediator gene expression during inflammation.
  • IL-22-induced MUC13 expression impaired barrier function via JAK1/STAT3, SNAI1/ZEB1, and ROCK2/MAPK pathways, with MUC1 cooperation.
  • MUC13 was protective in acute DSS colitis but detrimental in chronic colitis; associated pathways were altered in IBD patients.

Conclusions:

  • Aberrant MUC13 signaling actively induces intestinal barrier dysfunction during inflammation.
  • MUC1 acts as a collaborating partner with MUC13 in promoting barrier dysfunction.
  • These findings highlight MUC13 as a potential therapeutic target for IBD.
Keywords:
inflammationintracellular signalingtight junctiontransmembrane mucin

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