Levels of Components of the Urokinase-Type Plasminogen Activator System are Related to Chronic Obstructive Pulmonary Disease Parenchymal Destruction and Airway Remodelling

Abstract

OBJECTIVE: Retrospective study to investigate levels of components of the urokinase-type plasminogen activator (uPA) system in patients with chronic obstructive pulmonary disease (COPD). METHODS: Peripheral lung tissue was obtained from patients who underwent surgical resection for benign lung diseases: 16 patients with COPD, 10 controls without lung function impairment who were smokers, and 10 controls without lung function impairment who were nonsmokers.Immunohisto chemical staining for uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) was quantified. Airway remodelling (collagen; detected by Sirius red staining), lung function (determined by spirometry) and emphysema (alveolar destruction; percentage of low attenuation areas on computed tomography scan) were evaluated. RESULTS: uPA, uPAR and PAI-1 were significantly different in structural lung cells and pulmonary macrophages from patients with COPD compared with controls. There were significant positive correlations between collagen levels and uPA and PAI-1, and between uPA and degree of emphysema. There were significant inverse correlations between lung function and uPA, uPAR and PAI-1. CONCLUSION: Correlations between components of the uPA system and lung function, small airway fibrosis and emphysema indicate a role for the uPA system in COPD.

Involvement of urokinase in cigarette smoke extract-induced epithelial–mesenchymal transition in human small airway epithelial cells

“…The relationship between uPA expression in the epithelium and small airway remodeling requires further investigation, but relating epithelial histology to uPA expression in a crosssectional study would be difficult to interpret. Our previous studies found that uPA staining increased in the small airway 15 This study is the first to investigate the uPA protein expression ex vivo in the small airways of a number of control and COPD individuals. These findings provide a basis for further investigation of the role of uPA in the epithelium.…”

“…The elevated levels of uPAR in small airway epithelia and alveolar wall cells were also observed in COPD patients with a significant emphysema in our previous study. 15 Lungs from uPAR( À / À ) mice displayed nonspecific interstitial pneumonia-like pathological features, with a significant increase in alveolar septal width and collagen content. 36 These studies suggest that downregulation of uPAR may be related with interstitial pulmonary fibrosis; however, the uPAR-initiated EMT in small airway of COPD patients may be accounting for small airway fibrosis in COPD.…”

“…The immunohistochemical staining of uPA and uPAR is significantly elevated in the small airway epithelia of COPD patients compared with that of the controls. 15 Gene network search analysis shows numerous pathways that are biologically plausible candidates for COPD pathogenesis. For example, plasminogen activator, urokinase (PLAU); plasminogen activator, urokinase receptor; and thrombospondin (THBS1) are three genes involved in TGFb1 activation and matrix metalloproteinases (MMPs).…”

Soluble urokinase-type plasminogen activator receptor (suPAR) in multiple respiratory diseases

“…suPAR can convert plasminogen to plasmin, which degrades fibrin, activates matrix metalloproteases and mediates proteolysis of extracellular matrix proteins during cellular invasion [4] . suPAR modulate the functions of integrins (including activating intracellular signals, monocyte chemotaxis, cell adhesion and proliferation) [4,5] . So suPAR contributes to cell adhesion, migration, proliferation inflammation, chemotaxis, proteolysis, immune system activation, tissue remodeling and signal transduction [5,6] .…”

“…suPAR modulate the functions of integrins (including activating intracellular signals, monocyte chemotaxis, cell adhesion and proliferation) [4,5] . So suPAR contributes to cell adhesion, migration, proliferation inflammation, chemotaxis, proteolysis, immune system activation, tissue remodeling and signal transduction [5,6] . Several studies have identified that suPAR level is a important marker in patients with various diseases and associated with a poorer outcome in a range of non-infectious and infectious diseases [2] .…”