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Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis
M S Pepper1, R Montesano, S J Mandriota
1Department of Morphology, University of Geneva Medical Center, Switzerland.
Enzyme & Protein
|January 1, 1996
Summary
The plasminogen activator (PA)/plasmin system is crucial for extracellular proteolysis in angiogenesis. However, studies on deficient mice suggest its role may be limited to fibrin degradation during capillary sprouting.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Extracellular proteolysis regulates matrix degradation and cytokine activity during angiogenesis.
- The plasminogen activator (PA)/plasmin system, including urokinase-type PA (uPA), uPA receptor (uPAR), and PA inhibitor-1 (PAI-1), is expressed by endothelial cells during angiogenesis.
- In vitro studies suggested capillary morphogenesis depends on a protease-antiprotease equilibrium.
Purpose of the Study:
- To reevaluate the role of the PA/plasmin system in angiogenesis.
- To investigate the necessity of the PA/plasmin system for normal developmental and physiological angiogenesis.
Main Methods:
- Analysis of findings from uPA-, uPAR-, PAI-1, and plasminogen-deficient mice.
- Comparison of in vivo and in vitro observations regarding angiogenesis and the PA/plasmin system.
Main Results:
- Developmental and physiological angiogenesis occurred normally in mice deficient in uPA, uPAR, PAI-1, and plasminogen.
- These findings challenge the established notion of the PA/plasmin system's critical role in general angiogenesis.
Conclusions:
- The role of the PA/plasmin system in angiogenesis may be more specialized than previously thought.
- The PA/plasmin system might be primarily involved in situations requiring endothelial cell-mediated fibrin degradation for capillary sprout formation.