Matrilysin (MMP-7) catalytic activity regulates β-catenin localization and signaling activation in lung epithelial

Cliff R Rims1, John K McGuire

  • 1Department of Pediatrics and Center for Lung Biology, University of Washington , Seattle, Washington , USA.

Insights

Matrix metalloproteinase-7 (MMP-7) regulates β-catenin by releasing it from cell junctions, impacting its signaling. This finding links extracellular proteolysis to intracellular signaling in injured lung epithelium.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pulmonary Medicine

Background:

  • Matrix metalloproteinase-7 (MMP-7), also known as matrilysin, is upregulated in epithelial tissues during bacterial infection, inflammation, fibrosis, and various carcinomas.
  • MMP-7 degrades extracellular matrix and E-cadherin, facilitating wound healing and tissue remodeling.
  • β-catenin is crucial for adherens junctions and intracellular signaling.

Purpose of the Study:

  • To investigate if MMP-7-mediated adherens junction disassembly influences β-catenin localization and signaling.
  • To assess the impact of MMP-7 catalytic activity on β-catenin in A549 cells and a mouse model of lung injury.

Main Methods:

  • Assessed β-catenin localization and signaling activity in A549 cells treated with MMP-7.
  • Utilized a bleomycin-induced lung injury model in wild-type and matrilysin-null mice.
  • Measured β-catenin release, degradation, nuclear translocation, and promoter activation.

Main Results:

  • MMP-7 activity releases cell membrane-bound β-catenin, leading to its cytosolic degradation.
  • In the presence of Wnt signaling, MMP-7 activity causes β-catenin accumulation and activation of a β-catenin luciferase promoter.
  • Matrilysin-null mice exhibited impaired β-catenin nuclear translocation and activation following bleomycin-induced lung injury compared to wild-type mice.

Conclusions:

  • MMP-7 acts as a regulator of β-catenin function in injured lung epithelium.
  • Extracellular proteolytic activity, specifically MMP-7, can influence cell junction integrity and intracellular signaling pathways.
  • These findings establish a link between MMP-7, cell junction disassembly, and β-catenin-mediated signaling in the context of lung injury.

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