Related Experiment Video
Updated: Aug 24, 2025

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
Published on: May 26, 2021
Matrix metalloproteinase 7 contributes to intestinal barrier dysfunction by degrading tight junction protein
Ying Xiao1,2, Haifeng Lian3, Xiaoying S Zhong2
1Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.
Background:
Previous studies implicated matrix metalloproteinases (MMPs), such as MMP-7, in inflammatory bowel diseases (IBD) by showing increased activity during inflammation of the gut. However, the pathophysiological roles of MMP-7 have not been clearly elucidated.
Methods:
The expression of MMP-7 was assessed in colonic biopsies of patients with ulcerative colitis (UC), in rodents with experimental colitis, and in cell-based assays with cytokines. Wild-type and MMP-7-null mice treated with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid were used for determining the pro-inflammatory function(s) of MMP-7 in vivo.
Results:
MMP-7 was highly expressed in patients with UC and in rodents with experimental colitis. IL-1β, IL-4, IL-13, TNFα, or lipopolysaccharide enhanced MMP-7 expression in human colonic epithelial cells, rat colonic smooth muscle cells, and THP-1-derived macrophages. Active MMP-7 degraded tight junction protein Claudin-7 in epithelial cells, cleaved recombinant Claudin-7 in cell-free system, and increased Caco-2 monolayer permeability. Immunostaining of colon biopsies revealed up-regulation of MMP-7 and reduction of Claudin-7 in UC patients. Compared to wild-type mice, Mmp7 -/- mice had significantly less inflammation in the colon upon DSS insult. DSS-induced alterations in junction proteins were mitigated in Mmp7 -/- mice, suggesting that MMP-7 disrupts the intestinal barrier. MMP-7 antibody significantly ameliorated colonic inflammation and Claudin-7 reduction in 2 different rodent models of colitis.
Summary:
MMP-7 impairs intestinal epithelial barrier by cleavage of Claudin-7, and thus aggravating inflammation. These studies uncovered Claudin-7 as a novel substrate of MMP-7 in the intestinal epithelium and reinforced MMP-7 as a potential therapeutic target for IBD.
Insights
Matrix metalloproteinase-7 (MMP-7) exacerbates inflammatory bowel disease by degrading Claudin-7 and damaging the intestinal barrier. Targeting MMP-7 offers a potential therapeutic strategy for IBD.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs), including MMP-7, are implicated in inflammatory bowel diseases (IBD).
- The precise pathophysiological roles of MMP-7 in IBD pathogenesis remain unclear.
Purpose of the Study:
- To elucidate the role of MMP-7 in the pathogenesis of ulcerative colitis (UC).
- To investigate MMP-7 as a potential therapeutic target for IBD.
Main Methods:
- Assessed MMP-7 expression in colonic biopsies from UC patients and rodents with experimental colitis.
- Utilized wild-type and MMP-7-null mice in dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid models of colitis.
- Investigated the effect of MMP-7 on tight junction proteins and intestinal permeability in vitro and in vivo.
Main Results:
- MMP-7 expression was significantly upregulated in UC patients and experimental colitis models.
- Active MMP-7 degraded Claudin-7, increased intestinal permeability, and exacerbated colitis in wild-type mice.
- MMP-7-null mice exhibited reduced colonic inflammation and preserved intestinal barrier function.
- Antibody-mediated inhibition of MMP-7 ameliorated colitis in rodent models.
Conclusions:
- MMP-7 impairs the intestinal epithelial barrier by cleaving Claudin-7, thereby aggravating inflammation in IBD.
- Claudin-7 is identified as a novel substrate of MMP-7 in the intestinal epithelium.
- MMP-7 represents a promising therapeutic target for managing IBD.
Related Concept Videos
Tight Junctions
Role of Matrix Metalloproteases in Degradation of ECM
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Mucosal Barrier of the Stomach
Within parietal cells, carbonic acid is first formed through the reaction of water and carbon dioxide. The dissociation of carbonic acid releases bicarbonate and hydrogen ions. The bicarbonate...
Overview of Cell-Matrix Interactions
The Extracellular Matrix

