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

Background/aims-Alterations in synthesis and breakdown of extracellular mat rix components are known to play a crucial role in tissue remodelling durin g inflammation and wound healing. Degradation of collagens is highly regula ted 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 i nflammatory bowel disease (IBD). Patients/methods-mRNA expression was measured by quantitative competitive p olymerase chain reaction (PCR) in biopsies from patients with ulcerative co litis (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 inflam ed, 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 corr elated well with the histological degree of acute inflammation, resulting i n more than 15-fold increased MMP-1 and MMP-3 mRNA levels in inflamed versu s normal colon samples from patients with ulcerative colitis and Crohn's di sease. Conclusion-Profound overexpression of MMP-1 and MMP-3 mRNA transcripts sugg ests an important role for these enzymes in the process of tissue remodelli ng and destruction in inflammatory bowel disease.