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Equine laminitis: membrane type matrix metalloproteinase-1 (MMP-14) is involved in acute phase onset

M T Kyaw-Tanner1, O Wattle, A W van Eps

  • 1Australian Equine Laminitis Research Unit, School of Veterinary Science, Faculty of Natural Resources Agriculture and Veterinary Science, The University of Queensland, Brisbane, Queensland 4072, Australia.

Equine Veterinary Journal
|January 8, 2008
PubMed
Abstract

Insights

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in equine laminitis. MMP-14 levels decrease, while TIMP-2 levels increase during laminitis, suggesting a role for these enzymes in hoof disease.

Area of Science:

  • Equine pathology
  • Molecular biology
  • Biochemistry

Background:

  • Enzymatic processes at the hoof lamellar dermal-epidermal interface may contribute to laminitis development.
  • Understanding matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in lamellar tissues is crucial for elucidating laminitis pathogenesis.

Purpose of the Study:

  • To clone and sequence equine lamellar MMP-14 and TIMP-2 cDNA.
  • To quantify MMP-14 and TIMP-2 gene transcription in normal and laminitic equine hoof tissues.
  • To develop an antibody for localizing MMP-14 protein in lamellar tissues.

Main Methods:

  • Tissue samples from an oligofructose-induced equine laminitis model were used.
  • RNA isolation, RT-PCR amplification, cloning, sequencing, and real-time PCR were performed for gene expression analysis.
  • Antibody development and immunohistochemistry were employed to detect MMP-14 protein localization.

Main Results:

  • MMP-14 was detected in the cytoplasm of normal lamellar basal cells near the basement membrane.
  • MMP-14 immunostaining was reduced in lamellar basal cells of laminitic tissues.
  • MMP-14 and TIMP-2 gene expression were significantly elevated and lowered, respectively, in laminitic tissues.

Conclusions:

  • MMP-14, normally present in lamellar basal cell cytoplasm, is depleted during laminitis development.
  • Laminitis pathology is associated with increased MMP-14 and decreased TIMP-2 gene transcription.
  • Enzymes play a role in laminitis, and their inhibition could be a potential therapeutic strategy.

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