Plasminogen activation by airway smooth muscle is regulated by type I collagen

Abstract

Plasmin, the activated protease product of plasminogen, is involved in collagen remodeling, and is strongly implicated in asthma pathophysiology by recent genome-wide association studies. This study examines plasminogen "activation" by airway smooth muscle cells, and its regulation in a fibrotic environment created by culture on type I collagen and incubation with transforming growth factor (TGF)-β. Urokinase plasminogen activator (uPA) activity was detected in the supernatants of human airway smooth muscle cell cultures maintained in serum-free conditions. Incubation with plasminogen (1.5-50.0 μg/ml, 24 h) increased plasmin activity in a concentration- dependent manner (P < 0.001). uPA acti..