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The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity

de Laat, M.A, Kyaw-Tanner, M.T , Nourian, A.R , McGowan, C.M , Sillence, M.N, & Pollitt, C.C (2011) The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity. Veterinary Immunology and Immunopathology, 140(3-4), pp. 275-281.

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Abstract

Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.

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ID Code: 52106
Item Type: Journal Article
Keywords: Equine Laminitis MMP Hyperinsulinaemia Horse ADAMTS
DOI: 10.1016/j.vetimm.2011.01.013
ISSN: 0165-2427
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > ZOOLOGY (060800)
Australian and New Zealand Standard Research Classification > AGRICULTURAL AND VETERINARY SCIENCES (070000) > FISHERIES SCIENCES (070400)
Australian and New Zealand Standard Research Classification > AGRICULTURAL AND VETERINARY SCIENCES (070000) > VETERINARY SCIENCES (070700)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2011 Elsevier BV
Deposited On: 19 Jul 2012 16:27
Last Modified: 04 May 2013 09:36

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