Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter

G. Haddock, A. K. Cross, J. Plumb, J. Surr, D. J. Buttle, R. A D Bunning, M. N. Woodroofe

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    ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-1, -4 and -5 proteases have been identified in the CNS at the mRNA level. These glutamyl endopeptidases, inhibited by tissue inhibitor of metalloproteinases (TIMP)-3, are key enzymes in the degradation of the aggregating chondroitin sulphate proteoglycans (CSPGs), and may therefore play a role in CNS extracellular matrix (ECM) changes in multiple sclerosis (MS). We have investigated ADAMTS and TIMP-3 expression in normal and MS CNS white matter by real-time RT-PCR, western blotting and immunohistochemistry. We report for the first time the presence of ADAMTS-1, -4 and -5 in normal and MS white matter. Levels of ADAMTS-1 and -5 mRNA were decreased in MS compared to normal tissue, with no significant change in ADAMTS-4 mRNA levels. Protein levels of ADAMTS-4 were significantly higher in MS tissue compared to normal tissue. Immunohistochemical studies demonstrated that ADAMTS-4 was associated predominantly with astrocytes with increased expression within MS lesions. TIMP-3 mRNA was significantly decreased in MS compared to controls. These studies suggest a role for ADAMTS-4 in the pathogenesis of MS. Further studies on the activity of ADAMTS-4 will enable a better understanding of its role in the turnover of the ECM of white matter in MS. © 2006 Edward Arnold (Publishers) Ltd.
    Original languageEnglish
    Pages (from-to)386-396
    Number of pages10
    JournalMultiple Sclerosis
    Issue number4
    Publication statusPublished - Aug 2006


    • ADAMTS
    • Extracellular matrix
    • Multiple sclerosis
    • TIMP-3


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