Urokinase induces expression of its own receptor in Beas2B lung epithelialcells

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.