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.

Frontiers in Immunology
|October 24, 2022
PubMed
Abstract

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.

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