ИСТИНА

Introduction. Experimental findings indicate significant contribution of urokinase and urokinase receptor (uPA and uPAR) to the extracellular matrix degradation as part of nerve regeneration, however, its role in the nervous system during neural cell migration, axonal growth and branching is unclear. Using differentiated into neurons Neuro 2a cells (N2a), mouse Dorsal Root Ganglia (DRG) explants in 3-dimentional Matrigels and transgenic mice lacking urokinase gene (plau-/-) we studied the involvement of uPA/uPAR system in neural cell migration and neurite outgrowth, elongation and branching. Results. uPA and uPAR are expressed in the growth cones of axons in DRG and N2a cells. Using ex vivo DRG explants we found that uPA inhibition attenuates neural cell migration and axonal growth, pointing to an important role of uPA in these processes. Apparently, uPA mediates its effects through interaction with uPAR: blocking of uPAR by specific antibody, which blocks the uPA binding to uPAR, results in stimulation of axon branching and attenuates neural cell migration from DRG explants. Both, inhibition of uPA and uPAR almost completely prevents neural cell migration and axonal outgrowth from DRG into Matrigels. Using N2a differentiated into neurons we demonstrate that exogenous uPA (10 ng/ml) increases the neurite growth rate (elongation), most likely via interaction of uPA with uPAR. Blocking of uPAR stimulates neurite formation and enhances branching of preexisting neurites. The results obtained on DRG explants from plau-/- mice support the assumption that uPA stimulates neurite growth via its interaction with uPAR, and uPAR plays and important role in axon branching and neural cell migration. Conclusion. uPA and uPAR plays an important role in neural cell migration; urokinase system affects neuron morphology via regulation of axonal growth and branching.