ИСТИНА

Urokinase plasminogen activator was proved to stimulate angiogenesis, especially in ischemic tissue. At the same time the expression of urokinase and tissue plasminogen activators is elevated in neurons and Schwann cells after nerve injury. Since blood vessels and nerves are often co-localized we suggested that urokinase plasminogen activator could stimulate growth and restoration of nerve endings. To test this hypothesis we constructed pVax1-based plasmid containing optimized cDNA of mouse urokinase plasminogen activator (muPA). During surgery murine common peroneal nerve was crushed and the solution of pVax-muPA plasmid was transcutaneously injected into the tibialis anterior muscle (this muscle is innervated by nerve endings of the common peroneal nerve). In vitro tests confirmed stable and potent secretion of muPA by muscle cells for at least 7 days after transfection. During our study we found that gene thansfer of muPA to denervated muscle stimulates regeneration of nerve structure and conductivity compared to control vector (pVax). Our findings were confirmed by histological studies which showed increased number of NF200-positive structures in nerves taken from muPA gene transfer group and by electrophysiological studies which revealed faster conductivity and larger amplitude of the compound nerve action potentials. Taken together our data demonstrate that transfer of gene encoding urokinase plasminogen activator can be used to enhance regeneration of injured nerve fibers. Stimulation of nerve regeneration might be caused by urokinase plasminogen activator ability to stimulate angiogenesis in crushed nerve and denervated muscle, to degrade fibrin (nerve cone growth inhibitor) and extracellular matrix, to activate growth factors (by itself or via plasminogen activation) and to drive migration of nerve endings.