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Membrane-type matrix metalloproteinases in human dermal microvascular endothelial cells: expression and morphogenetic

V T Chan1, D N Zhang, U Nagaravapu

  • 1Department of Dermatology, Stanford University School of Medicine, California 94305, USA.

The Journal of Investigative Dermatology
|December 18, 1998
PubMed

Insights

Membrane-type matrix metalloproteinases (MT-MMP) are present in skin endothelial cells and play a role in new blood vessel formation. Blocking MT-MMP activity reduced cell movement and tubule formation in collagen gels.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Angiogenesis Research

Background:

  • Membrane-type matrix metalloproteinases (MT-MMP) are cell surface enzymes crucial for extracellular matrix remodeling.
  • MT-MMP activate proMMP-2, a key enzyme in tissue invasion, and are typically found in invasive tumors.
  • Understanding MT-MMP in non-malignant cells with transient invasive properties, like during angiogenesis, is important.

Purpose of the Study:

  • To identify and characterize MT-MMP expression and function in human dermal microvascular endothelial cells (HDMEC).
  • To investigate the role of MT-MMP in the invasive phenotype of HDMEC during angiogenesis.
  • To explore the modulation of MT-MMP by angiogenic factors and its effect on endothelial cell behavior.

Main Methods:

  • HDMEC were isolated and purified.
  • Reverse transcriptase-polymerase chain reaction and northern blotting were used to detect MT-MMP transcripts.
  • Immunoblotting and in vitro enzyme assays were performed to characterize MT-MMP protein forms and activity.
  • Cellular invasion and tubule formation assays in 3D collagen gels were conducted with and without MT-MMP inhibition.

Main Results:

  • MT-MMP-1 and -3 transcripts were detected in HDMEC, with MT-MMP-1 mRNA modulated by angiogenic factors.
  • Multiple processed forms of MT-MMP-1 were identified in HDMEC extracts.
  • HDMEC membranes activated proMMP-2 and proMMP-9, with anti-MT-MMP-1 antibodies specifically inhibiting proMMP-2 activation.
  • Inhibition of MT-MMP-1 significantly delayed HDMEC migration and tubule formation in 3D collagen gels.

Conclusions:

  • This study demonstrates the presence and functional activity of MT-MMP in cutaneous microvascular endothelial cells.
  • MT-MMP expression is modulated by angiogenic factors, suggesting a role in angiogenesis.
  • MT-MMP activity is critical for HDMEC morphogenetic patterns, including cell movement and tubule formation, highlighting their potential role in skin neovascularization.

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