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Gut 47:63-73 doi:10.1136/gut.47.1.63
  • Inflammation and inflammatory bowel disease

Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease

Abstract

BACKGROUND/AIMS Alterations in synthesis and breakdown of extracellular matrix components are known to play a crucial role in tissue remodelling during inflammation and wound healing. Degradation of collagens is highly regulated by a cascade of matrix metalloproteinases (MMPs). The current study was therefore designed to determine gene expression patterns of MMPs and their tissue inhibitors (TIMPs) in single endoscopic biopsies of patients with inflammatory bowel disease (IBD).

PATIENTS/METHODS mRNA expression was measured by quantitative competitive polymerase chain reaction (PCR) in biopsies from patients with ulcerative colitis (n=21) and Crohn's disease (n=21). Protein expression was analysed by western blotting and immunohistochemistry.

RESULTS MMP-2, MMP-14, and TIMP-1 mRNAs were marginally increased in inflamed, but 9–12-fold increased in ulcerated colonic mucosa in IBD whereas TIMP-2 mRNA expression remained unchanged. MMP-1 and MMP-3 mRNA expression correlated well with the histological degree of acute inflammation, resulting in more than 15-fold increased MMP-1 and MMP-3 mRNA levels in inflamed versus normal colon samples from patients with ulcerative colitis and Crohn's disease.

CONCLUSION Profound overexpression of MMP-1 and MMP-3 mRNA transcripts suggests an important role for these enzymes in the process of tissue remodelling and destruction in inflammatory bowel disease.

Footnotes

  • Abbreviations used in this paper:
    MMP
    matrix metalloproteinase
    MT-MMP
    membrane-type MMP
    TIMP
    tissue inhibitor of matrix metalloproteinases
    PCR
    polymerase chain reaction
    IBD
    inflammatory bowel disease
    ECM
    extracellular matrix
    CD
    Crohn's disease
    UC
    ulcerative colitis
    mRNA
    messenger RNA
    cDNA
    complementary DNA
    APAAP
    alkaline phosphatase/anti-alkaline phosphatase
    RT
    reverse transcription
    PVDF
    polyvinyldifluoride
    ECL
    enhanced chemiluminescence