Interaction between the urokinase-type plasminogen activator (uPA) and its
receptor (uPAR) localizes cellular proteolysis and promotes cellular prolif
eration and migration. The interaction between uPA and uPAR at the surface
of epithelial cells thereby contributes to the pathogenesis of lung inflamm
ation and neoplasia. In this study, we sought to determine if uPA itself al
ters uPAR expression by lung epithelial cells. uPA enhanced uPAR expression
as well as I-125-UpA binding in Beas2B lung epithelial cells in a time- an
d concentration-dependent manner. The uPA-mediated induction of uPAR is not
accomplished through its receptor and requires enzymatic activity. The low
molecular weight fragment of uPA, lacking the receptor binding domain, was
as potent as intact two-chain uPA in inducing expression of uPAR at the ce
ll surface. Plasmin, the end product of plasminogen activation, did not alt
er uPA-mediated uPAR expression. Induction of uPAR by uPA represents a nove
l pathway by which epithelial cells can regulate uPAR-dependent cellular re
sponses that may contribute to stromal remodeling in lung injury or neoplas
ia.