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

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 maj or matrix degrading proteases, matrix metalloproteinase (MMP)-1 and MMP-3, their inhibitor, tissue inhibitor of metalloproteinases (TIMP)-1, and proco llagen 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 w ere hybridised with S-35-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 MMMP-1 (p<0.005), MMP-3 (p<0.01), and TIMP-1 (p<0.05) mRNA were higher in the subepithelial region of CD muc osa 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 re mained elevated. The number of procollagen I mRNA expressing cells did not change. Expression of MMP-1 and MMP-3 mRNA was mainly localised to subepith elial fibroblasts and macrophages. Conclusions-The decreased ratio of collagen I and TIMP-1 mRNA expressing ce lls to MMP-1 and MMP-3 mRNA expressing cells in untreated CD suggests a shi ft towards ECM degradation. ECM degradation by activated subepithelial fibr oblasts and macrophages may be an important mechanism driving mucosal trans formation in CD.