title: Oxidative stress, plasminogen activator inhibitor 1, and lung fibrosis.
abstract: 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.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. rliu@uab.edu
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism* / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000453:epidemiology / Q000503:physiopathology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1