MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve.
Compared to degenerated nerves, the ability of normal adult peripheral nerve to support axonal regeneration is poor and may be attributed to the inhibition of endoneurial laminin by chondroitin sulfate proteoglycan (CSPG). In cryoculture assays, neuritic growth of neonatal and adult peripheral neurons was increased on sections of normal nerve by pretreatment with CSPG-degrading enzymes, including the matrix metalloproteinases MMP-2 and MMP-9. Axonal regeneration is known to occur within the Schwann cell basal laminae of degenerated nerve. Similarly, deconvolution microscopy revealed that neuritic growth on nerve tissue sections occurred principally on the lumenal surface of enzymatically modified basal laminae. Compared to normal nerve, there was a marked increase in the neurite-promoting activity of the degenerated nerve, and this activity was not increased significantly by subsequent MMP treatment. Additionally, the expression and activation of MMP-2 and MMP-9 were elevated in degenerated nerve, suggesting that degradation of inhibitory CSPG by the MMPs contributes to the growth-promoting properties of degenerated nerve.
Division of Neurology, University of Florida Brain Institute and College of Medicine, Gainsville, Florida 32610-0296, USA.
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Ferguson
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Muir
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D006820:Hyaluronic Acid / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000201:enzymology*; D009474:Neurons / Q000166:cytology; D010525:Peripheral Nerves / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000201:enzymology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D014855:Wallerian Degeneration / Q000378:metabolism*
D006820:Hyaluronic Acid; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9