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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
Summary
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.