INCREASED AXON GROWTH THROUGH ASTROCYTE CELL-LINES TRANSFECTED WITH UROKINASE

The ability of cells to migrate through tissues depends on their produ ction of a variety of proteases, and the same may be true of growth co nes. Urokinase (plasminogen activator) regulates much of the extracell ular proteolytic activity, by activating other proteases and as a resu lt of its own proteolytic activity. In order to evaluate the potential role of urokinase as a promoter of axon growth, we have used a plasmi d expressing urokinase under a cytomegalovirus promoter to transfect a n astrocyte cell line, Neu7, which we have previously shown to provide a poor environment for axon regeneration. Five transfected lines all showed greatly increased ability to promote axon regeneration in both monolayer and three-dimensional cultures. The critical change in the t ransfected cells was largely within the extracellular matrix, since ex tracellular matrix laid down by urokinase-secreting cells was more per missive to axon growth than matrix from the parent Neu7 line. The effe ct was due to urokinase since treatment of the transfected cells with the urokinase inhibitors B623 and B428 rendered both the cells and the ir matrix much less permissive to axon growth, but did not require pla sminogen, since it was blocked neither by serum-free medium nor by pla smin inhibitors. (C) 1998 Wiley-Liss, Inc.