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MMP-2 and MMP-9 Increase the Neurite-Promoting Potential of Schwann Cell Basal Laminae and Are Upregulated in Degenerated Nerve

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Abstract

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.

References (41)

  • Y.J. Son et al.

    Nerve sprouting in muscle is induced and guided by processes extended by Schwann cells

    Neuron

    (1995)
  • G.Y. Wang et al.

    The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts

    Brain Res.

    (1992)
  • T. Yamagata et al.

    Purification and properties of bacterial chondroitinases and chondrosulfatases

    J. Biol. Chem.

    (1968)
  • J. Zuo et al.

    Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue

    Exp. Neurol.

    (1998)
  • E. Agius et al.

    Comparison of neurite outgrowth induced by intact and injured sciatic nerves: A confocal and functional analysis

    J. Neurosci.

    (1998)
  • C.E. Bandtlow et al.

    Developmental changes in neuronal responsiveness to the CNS myelin-associated neurite growth inhibitor NI-35/250

    Eur. J. Neurosci.

    (1997)
  • K.S. Bedi et al.

    Adult rat dorsal root ganglion neurons extend neurites on predegenerated but not on normal peripheral nerves in vitro

    Eur. J. Neurosci.

    (1992)
  • J.L. Bixby et al.

    Molecular mechanisms of axon growth and guidance

    Annu. Rev. Cell Biol.

    (1991)
  • J.E. Bottenstein et al.

    Growth of a rat neuroblastoma cell line in serum-free supplemented medium

    Proc. Natl. Acad. Sci. USA

    (1979)
  • S. Carbonetto et al.

    Nerve fiber growth in culture on tissue substrata from central and peripheral nervous systems

    J. Neurosci.

    (1987)
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    To whom correspondence should be addressed at Pediatric Neurology, Box 100296, University of Florida College of Medicine, Gainesville, Florida 32610. Fax: (352) 392-9520. E-mail: [email protected].

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