Related Experiment Video

Updated: May 11, 2026

Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
09:24

Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model

Published on: February 11, 2021

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating

Roosmarijn E Vandenbroucke1, Eline Dejonckheere, Filip Van Hauwermeiren

  • 1Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

EMBO Molecular Medicine
|June 1, 2013
PubMed

Insights

Matrix metalloproteinase MMP13 deficiency protects against sepsis and inflammatory bowel disease (IBD) by reducing gut barrier damage. MMP13 acts as a TNF sheddase, making it a potential drug target for gastrointestinal diseases.

Area of Science:

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background:

  • Intestinal epithelial barrier dysfunction is implicated in sepsis and inflammatory bowel disease (IBD).
  • Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and inflammation.
  • The specific role of MMP13 in intestinal diseases remains largely unexplored.

Purpose of the Study:

  • To investigate the role of matrix metalloproteinase 13 (MMP13) in the pathogenesis of sepsis and IBD.
  • To determine if MMP13 contributes to intestinal barrier damage in these conditions.
  • To explore MMP13 as a potential therapeutic target for gut diseases.

Main Methods:

  • Mice lacking MMP13 (MMP13(-/-)) and wild-type (MMP13(+/+)) littermates were used in models of sepsis (LPS-induced and caecal ligation/puncture) and colitis (DSS-induced).
  • Intestinal barrier function, goblet cell depletion, endoplasmic reticulum stress, and tight junction integrity were assessed.
  • In vitro and in vivo assays were performed to determine MMP13's enzymatic activity on pro-tumor necrosis factor (pro-TNF).
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify MMP13 cleavage sites on pro-TNF.

Main Results:

  • MMP13(-/-) mice showed significant protection against sepsis and DSS-induced colitis compared to MMP13(+/+) mice.
  • Protection in MMP13(-/-) mice was associated with reduced goblet cell depletion, endoplasmic reticulum stress, permeability, and improved tight junction stability.
  • MMP13 was identified as an alternative TNF sheddase capable of cleaving pro-TNF into bioactive TNF, with three specific cleavage sites identified.
  • The mechanism of MMP13-mediated TNF shedding was found to be responsible for the observed protection in both sepsis and colitis models.

Conclusions:

  • MMP13 plays a critical role in mediating intestinal damage during sepsis and IBD.
  • MMP13 facilitates the shedding of TNF, contributing to disease pathogenesis.
  • MMP13 represents a novel and promising therapeutic target for managing gut damage in sepsis and inflammatory bowel disease.
Keywords:
IBDintestinal permeabilitymatrix metalloproteinasesepsistumour necrosis factor

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