MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites.
Scar formation following adult spinal cord (SC) hemisection is accompanied by important remodeling of the surrounding extracellular matrix (ECM). Since ECM molecules provide the substrate for axon growth, these changes in ECM composition are likely to influence the process of axonal regeneration. Here we investigated whether scar formation could be associated with the activation of matrix metalloproteinases (MMPs), a class of proteins implicated in ECM remodeling thought to favor axonal regeneration in the peripheral nervous system. Two members of the MMP family, MMP-2 and MMP-9, were found to be transiently upregulated in the SC wound. In situ fluorescent zymography revealed a MMP-related gelatinase activity (GA) in the wound, which was spatially and temporally correlated with scar formation. The GA formed a striking pattern of interwoven pathways along which neurites were seen to grow. These pathways corresponded to the distribution of other ECM molecules, which are known to have antagonistic effects on axonal regrowth. Our results suggest that neurite ingrowth into the wound may transiently benefit from this ECM remodeling and, in particular, from the upregulation of MMPs.
Duchossoy
Y
Y
Laboratoire de Neurobiologie, Université Paris V René Descartes, Paris, France.
Horvat
J C
JC
Stettler
O
O
D000375:Aging / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D019771:Axotomy; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000201:enzymology* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D011508:Chondroitin Sulfate Proteoglycans; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D016900:Neurofilament Proteins; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9