Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush.
Plasminogen activators (PAs), tissue PA (tPA) and urokinase PA (uPA), have been shown to be induced in sensory neurons after sciatic nerve crush. These findings suggested that PAs facilitate peripheral nerve regeneration by digesting adhesive cell contacts and by activation of other proteases, thereby initiating a proteolytic cascade. Both tPA and uPA activate some matrix metalloproteases (MMPs), indirectly via plasminogen activation or directly, such as the uPA activation of MMP-2. In this study, we demonstrated, by using tPA and uPA knockout mice, that a lack of a plasminogen activator affected MMP-9 and MMP-2 activity after crushing of the sciatic nerve. These findings show that the PAs are important for MMP-9 and MMP-2 activity at the crush site.
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Lisa B
LB
Siconolfi
Nicholas W
NW
Seeds
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009409:Nerve Crush / Q000379:methods; D012584:Sciatic Nerve / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9