urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies尿激酶纤溶酶原受体和纤溶复杂物在神经修复中发挥作用在小鼠神经粉碎后,在人类的疾病.pdf

Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies Cristina Rivellini1,2, Giorgia Dina1,2, Emanuela Porrello1,2, Federica Cerri1,2,3, Marina Scarlato1,2,3, Teuta 1,2 3 3 1,2,4 1,2,3 Domi , Daniela Ungaro , Ubaldo Del Carro , Alessandra Bolino , Angelo Quattrini , Giancarlo Comi1,2,3,5, Stefano C. Previtali1,2,3* 1 Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy, 2 Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, 3 Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, 4 Dulbecco Telethon Institute, Rome, Italy, 5 ‘‘Vita e Salute’’ San Raffaele University, Milan, Italy Abstract Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects ne