title: Urokinase receptor orchestrates the plasminogen system in airway epithelial cell function.
abstract: OBJECTIVE
  The plasminogen system plays many roles in normal epithelial cell function, and components are elevated in diseases, such as cancer and asthma. The relative contribution of each component to epithelial function is unclear. We characterized normal cell function in airway epithelial cells with increased expression of selected pathway components.
  
  
  METHODS
  BEAS-2B R1 bronchial epithelial cells stably overexpressing membrane urokinase plasminogen activator receptor (muPAR), soluble spliced uPAR (ssuPAR), the ligand (uPA) or inhibitors (PAI1 or PAI2), were characterized for pathway expression. Cell function was examined using proliferation, apoptosis, and scratch wound assays. A549 alveolar epithelial cells overexpressing muPAR were similarly characterized and downstream plasmin activity, MMP-1, and MMP-9 measured.
  
  
  RESULTS
  Elevated expression of individual components led to changes in the plasminogen system expression profile, indicating coordinated regulation of the pathway. Increased muPAR expression augmented wound healing rate in BEAS-2B R1 and attenuated repair in A549 cells. Elevated expression of other system components had no effect on cell function in BEAS-2B R1 cells. This is the first study to investigate activity of the splice variant ssuPAR, with results suggesting that this variant plays a limited role in epithelial cell function in this model.
  
  
  CONCLUSIONS
  Our data highlight muPAR as the critical molecule orchestrating effects of the plasminogen system on airway epithelial cell function. These data have implications for diseases, such as cancer and asthma, and suggest uPAR as the key therapeutic target for the pathway in approaches to alter epithelial cell function.
authors: Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, NG7 2UH, UK.
authors: Ceri E
authors: CE
authors: Stewart
authors: Ian
authors: I
authors: Sayers
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1