DISTINCT EXPRESSION PROFILES OF STROMELYSIN-2 (MMP-10), COLLAGENASE-3(MMP-13), MACROPHAGE METALLOELASTASE (MMP-12), AND TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP-3) IN INTESTINAL ULCERATIONS

Programed expression of matrix metalloproteinases is involved in wound healing in various organs, We have previously demonstrated enhanced e xpression of collagenase-1, stromelysin-1, matrilysin, and tissue inhi bitor of metalloproteinases (TIMP-1) in gastrointestinal ulcerations. To further define the role of matrix-degrading enzymes and their inhib itors in intestinal inflammation and ulcerations, the expression of st romelysin-2 (MMP-10), collagenase-3 (MMP-13), macrophage metalloelasta se (HME, MMP-12), and TIMP-3 mRNAs was studied using in situ hybridiza tion and immunohistochemistry in 38 samples representing ulcerative co litis, Crohn's disease, ischemic colitis, and normal intestine. As con trols for normally healing intestinal wounds, 12 postoperative samples of rat experimental jejunal anastomoses were also examined, The colit is types studied did not essentially differ in their MMP expression, W e found stromelysin-2 mRNA in laminin-5-positive and Ki-67-negative en terocytes bordering the ulcerations, HME was abundantly expressed by m acrophages in the vicinity of shedding mucosal epithelium and beneath the necrotic surface of the ulcers. Collagenase-3 and TIMP-3 were expr essed by fibroblast-like cells deeper in the remodeling intestinal wal l. Expression for stromelysin-2 and collagenase-3 was observed in gran ulation tissue, but not the epithelium, of the rat anastomoses. Our re sults suggest a role for stromelysin-2 in epithelial migration and for metalloelastase in macrophage movement and epithelial cell shedding.