Plasminogen Activator Inhibitor-1 in Asthma
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Abstract
Plasminogen activator inhibitor (PAI)-1 is a serine protease that, in addition to its major role in hemostasis, is known to play an essential role in tissue remodeling. Recent evidence indicates that chronic asthma may lead to tissue remodeling such as subepithelial fibrosis and extracellular matrix (ECM) deposition in the airways. However, the role of PAI-1 in asthma is unknown. Recently, we demonstrated that the mast cell (MC), which plays a major role in asthma, is a novel source of PAI-1 and a large number of MCs expressing PAI-1 are infiltrated in the airways of patients with asthma. Furthermore, PAI-1-deficient mice show reduced ECM deposition in the airways of a murine model of asthma. In a human study, the 4G allele frequency of the PAI-1 gene was significantly higher in the asthmatic patients than in the control group. In view of the findings that the 4G allele is associated with elevated plasma PAI-1 level, elevated PAI-1 level in the lung may contribute to the development of asthma. In conclusion, PAI-1 may play an important role in the pathogenesis of asthma by promoting ECM deposition in the airways of asthmatics.
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