Oxidative stress, plasminogen activator inhibitor 1, and lung fibrosis

Fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) in basement membranes and interstitial tissues, resulting from increased synthesis or decreased degradation of ECM or both. The plasminogen activator/plasmin system plays an important role in ECM degradation, whereas the plasminogen activator inhibitor 1 (PAI-1) is a physiologic inhibitor of plasminogen activators. PAI-1 expression is increased in the lung fibrotic diseases and in experimental fibrosis models. The deletion of the PAI-1 gene reduces, whereas the overexpression of PAI-1 enhances, the susceptibility of animals to lung fibrosis induced by different stimuli, indicating an important role of PAI-1 in the development of lung fibrosis. Many growth factors, including transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha), as well as other chemicals/agents, induce PAI-1 expression in cultured cells and in vivo. Reactive oxygen and nitrogen species (ROS/RNS) have been shown to mediate the induction of PAI-1 by many of these stimuli. This review summarizes some recent findings that help us to understand the role of PAI-1 in the development of lung fibrosis and ROS/RNS in the regulation of PAI-1 expression during fibrogenesis.