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uPA/plasmin system-mediated MMP-9 activation is implicated in bronchial epithelial cell migration
C Legrand1, M Polette, J M Tournier
1Laboratoire Pol Bouin-CHU, INSERM Unité 514, IFR 53, and, Reims, France.
Experimental Cell Research
|March 23, 2001
Summary
Urokinase plasminogen activator (uPA) drives human bronchial epithelial cell migration by generating plasmin. Plasmin then activates matrix metalloproteinase-9 (MMP-9), facilitating cell movement and wound repair.
Area of Science:
- Cell Biology
- Biochemistry
- Respiratory Medicine
Background:
- Cell migration is crucial for wound repair and tissue regeneration.
- The urokinase plasminogen activator (uPA)/plasmin system and matrix metalloproteinase-9 (MMP-9) are implicated in extracellular matrix remodeling and cell motility.
Purpose of the Study:
- To investigate the role of the uPA/plasmin system in human bronchial epithelial cell migration.
- To elucidate the relationship between uPA, plasmin, and MMP-9 activation in cell migration.
Main Methods:
- Utilized ex vivo and in vitro wound-repair models with human bronchial epithelial cells.
- Employed videomicroscopy for cell tracking and migration speed quantification.
- Assessed the impact of anti-uPA antibodies, plasmin, and activated MMP-9 on cell migration.
Main Results:
- uPA was localized at the wound edge in migrating cells, crucial for cell-matrix interactions.
- Inhibition of uPA reduced cell migration velocity by 70%.
- Plasmin and activated MMP-9 significantly increased cell migration velocity in a dose-dependent manner.
- Exogenous plasmin enhanced activated MMP-9 levels, and anti-uPA antibodies inhibited MMP-9 activation.
Conclusions:
- uPA plays a significant role in human bronchial epithelial cell migration.
- This migratory function is mediated by plasmin generation, which subsequently activates MMP-9.
- The uPA/plasmin/MMP-9 cascade is essential for facilitating bronchial epithelial cell migration.