UP-REGULATION OF UROKINASE RECEPTOR EXPRESSION ON MIGRATING ENDOTHELIAL-CELLS

One of the phenotypic hallmarks of migrating endothelial cells, both i n vivo and in vitro, is expression of the urokinase-type plasminogen a ctivator (u-PA), a key mediator of extracellular proteolysis. In the s tudy reported here, we have used an in vitro model of endothelial cell migration to explore the mechanism of this phenomenon. We have found that wounding of an endothelial cell monolayer triggers a marked, rapi d and sustained increase in expression of a specific high-affinity rec eptor for u-PA (u-PAr) on the surface of migrating cells. Migrating ce lls displayed an increase in the levels of u-PA and u-PAr mRNAs, and t his increase was mediated by endogenous basic fibroblast growth factor (bFGF). We also show that the increase in u-PA activity on migrating cells can be accounted for by an increase in receptor-bound u-PA, and that the increase in activity is also dependent on endogenous bFGF. Th ese results demonstrate that the expression of plasmin-mediated proteo lytic activity by migrating endothelial cells is a consequence of incr eased production of both u-PA and its receptor, and that this in tum i s mediated by endogenous bFGF. This suggests that u-PA, produced at in creased levels by migrating cells, binds to u-PAr whose expression is upregulated on the same cells. These observations are in accord with t he postulated role of u-PAr in mediating efficient and spatially restr icted extracellular proteolysis, particularly in the context of cell m igration.