PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model

CK Oh, B Ariue, RF Alban, B Shaw, SH Cho - Biochemical and biophysical …, 2002 - Elsevier
CK Oh, B Ariue, RF Alban, B Shaw, SH Cho
Biochemical and biophysical research communications, 2002Elsevier
Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are
associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated
plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by
inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-
1−/− and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition
of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after …
Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-1−/− and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after OVA challenge compared with saline challenge. However, in PAI-1−/− mice, collagen deposition was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold higher. This is the first direct evidence that the plasmin system regulates ECM deposition in the airways of a murine asthma model, independently of the effect of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM deposition occurs.
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