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Control of smooth muscle cell function by membrane-type matrix metalloproteinases

K I Shofuda1, D Hasenstab, T Shofuda

  • 1Department of Surgery, University of Washington School of Medicine, Seattle 98195-6410, USA.

Annals of the New York Academy of Sciences
|January 25, 2002
PubMed

Insights

Vascular smooth muscle cells (SMCs) overexpressing membrane-type matrix metalloproteinases (MT-MMPs) showed altered morphology, reduced adhesion, and increased migration. MT1-MMP enhanced MMP-2 activation more than MT3-MMP.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Vascular smooth muscle cells (SMCs) express membrane-type matrix metalloproteinases (MT-MMPs), specifically MT1-MMP and MT3-MMP.
  • Expression of these enzymes can be induced by platelet-derived growth factor (PDGF) in cell culture or by balloon injury in carotid arteries.

Purpose of the Study:

  • To elucidate the functional roles of MT1-MMP and MT3-MMP in vascular smooth muscle cells.
  • To investigate the effects of MT-MMP overexpression on MMP-2 activation, cell morphology, adhesion, and migration.

Main Methods:

  • Adenoviral vectors were used to transduce cDNAs for MT1-MMP and MT3-MMP into baboon-cultured SMCs, leading to overexpression.
  • Matrix metalloproteinase-2 (MMP-2) activation was assessed.
  • Cell morphology, adhesion to extracellular matrices, and migration (using a Boyden chamber assay) were evaluated.
  • The effect of a metalloproteinase inhibitor (BB94) was examined.

Main Results:

  • Overexpression of MT1-MMP significantly increased the conversion of proMMP-2 to its active form.
  • MT3-MMP overexpression resulted in only partial activation of MMP-2.
  • Both MT1-MMP and MT3-MMP overexpression induced morphological changes in SMCs, characterized by cell rounding.
  • These morphological alterations were reversible with the addition of BB94.
  • Cells exhibiting the rounded morphology demonstrated reduced adhesion to matrices and enhanced migratory capacity.

Conclusions:

  • MT1-MMP and MT3-MMP play significant roles in modulating vascular smooth muscle cell behavior.
  • Both MT-MMPs can induce phenotypic changes in SMCs, impacting cell adhesion and migration, potentially through MMP-2 activation.
  • These findings suggest MT-MMPs are involved in vascular remodeling processes.

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