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Published on: October 19, 2018

MMP9 modulates tight junction integrity and cell viability in human airway epithelia

Paola D Vermeer1, James Denker, Miriam Estin

  • 1Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|March 10, 2009
PubMed

Insights

Matrix metalloprotease-9 (MMP9) increases airway permeability in asthma by disrupting epithelial cell junctions. Tissue inhibitor of metalloprotease-1 (TIMP1) blocks these MMP9 effects, suggesting a therapeutic target for airway remodeling.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Immunology

Background:

  • Matrix metalloproteases (MMPs), zinc- and calcium-dependent enzymes, are implicated in airway remodeling in diseases like asthma.
  • Elevated MMP9 levels and decreased tissue inhibitor of metalloprotease-1 (TIMP1) in asthmatic airways suggest increased protease activity contributes to disease pathogenesis.

Purpose of the Study:

  • To elucidate the mechanism by which MMP9 contributes to asthma pathogenesis and airway remodeling.
  • To investigate the role of MMP9 in regulating human airway epithelial barrier function and integrity.

Main Methods:

  • Utilized a well-differentiated human airway epithelial model.
  • Assessed the impact of apical MMP9 on transepithelial conductance and tight junction protein expression.
  • Evaluated viral access to the basolateral surface and epithelial cell death following MMP9 treatment.
  • Investigated the inhibitory effect of TIMP1 on MMP9-induced changes.

Main Results:

  • Apical MMP9 significantly increased transepithelial conductance, indicating enhanced permeability.
  • MMP9 treatment disrupted tight junction proteins, compromising epithelial barrier function.
  • Increased viral access to the basolateral surface and heightened epithelial cell death were observed after MMP9 exposure.
  • TIMP1 effectively blocked all observed MMP9-mediated effects.

Conclusions:

  • MMP9 disrupts airway epithelial barrier integrity by cleaving cell-cell junction components, potentially triggering anoikis.
  • These findings suggest MMP9 directly regulates a component of airway remodeling in asthma.
  • TIMP1 acts as a key inhibitor of MMP9's detrimental effects on airway epithelium.

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