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Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease

Abstract

Background Extracellular matrix (ECM) degradation may play a role in villus atrophy in coeliac disease (CD).

Aims To compare the cellular expression of mRNA transcripts for the two major matrix degrading proteases, matrix metalloproteinase (MMP)-1 and MMP-3, their inhibitor, tissue inhibitor of metalloproteinases (TIMP)-1, and procollagen I in the intestinal mucosa of patients with untreated and treated CD and normal controls.

Patients/Methods Duodenal biopsy specimens from ten untreated CD patients, from six of these after a gluten free diet, and from ten control patients were hybridised with 35S-labelled RNA probes. The number of positive cells in the subepithelial region and lamina propria were counted microscopically.

Results The numbers of cells positive for MMP-1 (p<0.005), MMP-3 (p<0.01), and TIMP-1 (p<0.05) mRNA were higher in the subepithelial region of CD mucosa than in that from controls. In the lamina propria, only cells positive for MMP-1 mRNA were increased in CD patients compared with controls (p<0.01). MMP-1 and MMP-3 mRNA expression returned to normal in CD patients after treatment with a gluten free diet (p<0.05), while TIMP-1 mRNA expression remained elevated. The number of procollagen I mRNA expressing cells did not change. Expression of MMP-1 and MMP-3 mRNA was mainly localised to subepithelial fibroblasts and macrophages.

Conclusions The decreased ratio of collagen I and TIMP-1 mRNA expressing cells to MMP-1 and MMP-3 mRNA expressing cells in untreated CD suggests a shift towards ECM degradation. ECM degradation by activated subepithelial fibroblasts and macrophages may be an important mechanism driving mucosal transformation in CD.

  • coeliac disease
  • extracellular matrix
  • villus atrophy
  • matrix metalloproteinases
  • TIMP-1
  • collagen I
  • Abbreviations

    CD
    coeliac disease
    ECM
    extracellular matrix
    MMP
    matrix metalloproteinase
    TIMP
    tissue inhibitor of metalloproteinases
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  • Abbreviations

    CD
    coeliac disease
    ECM
    extracellular matrix
    MMP
    matrix metalloproteinase
    TIMP
    tissue inhibitor of metalloproteinases
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