Enhanced expression of matrilysin, collagenase, and stromelysin-1 in gastrointestinal ulcers

Programmed expression of several matrix metalloproteinases is an important feature of cutaneous wound healing. To study whether this also applies to gastrointestinal ulcer healing, we used in situ hybridization with 35S-labeled probes to localize sites of collagenase, stromelysin-1, and matrilysin expression in 26 samples representing peptic ulcers, Crohn's disease, and ulcerative colitis. In contrast to skin wounds, collagenase mRNA was not detected in the surface epithelium bordering gastrointestinal ulcer areas. However, together with stromelysin-1 mRNA, it was abundantly expressed by the granulation tissue in all types of ulcers. Signal for matrilysin mRNA and protein was detected in the mucosal epithelium bordering the ulcerations but never in the ulcer stroma. The gut basement membrane was disrupted under the matrilysin-producing epithelial cells as assessed by immunostaining for laminin. Tissue inhibitor of metalloproteinases (TIMP-1) mRNA never co-localized with matrilysin-positive mucosal epithelial cells. These data indicate that matrilysin plays a significant role in epithelial remodelling occurring in gastrointestinal ulcerations whereas collagenase and stromelysin-1 are involved in the reparative processes in the ulcer bed.