The plasminogen activation system: new targets in lung inflammation and remodeling

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HighlightsA strategy for treating chronic respiratory disease is to reduce airspace fibrin.Small molecule inhibitors of PAI-1 show beneficial effects in lung injury models.uPA is an important mediator of lung inflammation and remodeling in injury and disease.Preclinical characterization of uPA inhibitors as therapy for lung disease is required.The plasminogen activation system (PAS) and the plasmin it forms have dual roles in chronic respiratory diseases including asthma, chronic obstructive pulmonary disease and interstitial lung disease. Whilst plasmin-mediated airspace fibrinolysis is beneficial, interstitial plasmin contributes to lung dysfunction because of its pro-inflammatory and tissue remodeling activities. Recent studies highlight the potential of fibrinolytic agents, including small molecule inhibitors of plasminogen activator inhibitor-1 (PAI-1), as treatments for chronic respiratory disease. Current data also suggest that interstitial urokinase plasminogen activator is an important mediator of lung inflammation and remodeling. However, further preclinical characterization of uPA as a drug target for lung disease is required. Here we review the concept of selectively targeting the contributions of PAS to treat chronic respiratory disease.

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