Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur, Gyu Young; Broide, David H.

PLAUR, also known as uPAR or CD87, was originally identified as a proteinase receptor for urokinase plasminogen activator(uPA) concentrating plasmin proteolysis to the surface of migrating cells. 15 The uPA and uPAR have been associated with several inflammatory diseases including eosinophil recruitment in asthma. In asthmatics, airway eosinophils express significantly more uPA and uPAR protein compared to peripheral blood eosinophils. 16 Since PLAUR may also contribute to tissue remodeling via uPA-mediated plasmin proteolysis, 17 PLAUR has been proposed as a potential gene contributing to asthma development and airway remodeling. 18 PLAUR genetic polymorphisms, including SNPs rs2356338, rs4802189 and rs4803648 SNPs, are associated with a rapid decline in FEV1 in asthmatics. 18 In addition, these PLAUR genetic polymorphisms are associated with the features of airway remodeling, including basement membrane thickness, collagen III deposition and basal epithelial proliferation (% of Ki67 + cells) as quantitated using bronchial biopsy samples from asthmatic patients. 19 These results suggested that PLAUR SNPs may augment airway eosinophilic inflammation and airway structural changes, resulting in a more rapid lung function decline and airway remodeling in a subset of asthmatics.