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

HADDOCK, G., CROSS, A. K., PLUMB, J., SURR, J., BUTTLE, D. J., BUNNING, R. A. D. and WOODROOFE, M. N. (2005). Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Multiple Sclerosis, 12 (4), 386-396.

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Link to published version:: 10.1191/135248506ms1300oa

Abstract

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.

Item Type: Article
Uncontrolled Keywords: ADAMTS, extracellular matrix, multiple sclerosis, TIMP-3
Research Institute, Centre or Group: Biomedical Research Centre
Identification Number: 10.1191/135248506ms1300oa
Depositing User: Ann Betterton
Date Deposited: 20 Feb 2008
Last Modified: 24 Sep 2010 15:21
URI: http://shura.shu.ac.uk/id/eprint/426

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