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
Summary
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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