Wound healing is a process that results in restoration of the injured tissue. It involves re-epithelialization, granulation tissue formation and connective tissue remodeling. These events require controlled lysis of the extracellular matrix, important mediators of which are matrix metalloproteinases (matrixins, MMPs). MMPs comprise a group of enzymes that collectively are able to degrade most, if not all, components of the extracellular matrix (ECM). These enzymes are divided into subfamilies of collagenases, stromelysins, gelatinases, and MT-MMPs, based on their structure and substrate specificities. The expression of MMPs is controlled by cytokines, growth factors, oncogenes, and changes in the cell-cell and cell-matrix interactions. In the skin, the main cell types expressing these enzymes are keratinocytes, fibroblasts, macrophages, and endothelial cells. Tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3 and -4, are the most important inhibitors of MMPs, whose activities are required not only to prevent excessive proteolysis of tissues but also to regulate e.g. cell proliferation and angiogenesis. MMPs, controlled by their inhibitors, are involved in physiological processes such as reproduction and fetal development. An imbalance between MMPs and TIMPs has been implicated in abnormal tissue degradation leading to chronic wounds as well as cancer invasion and metastasis.
In this study, we investigated the cellular origin, and the temporal expression patterns of collagenases-1 and -3, stromelysins-1 and -2, matrilysin and macrophage metalloelastase in normally healing and chronic wounds of the skin. Furthermore, MMP-expression profiles in chronic, erosive and/or ulcerative lesions caused by inflammatory bowel disease (IBD), multifactorial disorders of the intestine, were studied. The inhibitors of MMPs, TIMPs, as well as various ECM proteins, were also examined in lesions of the skin and the intestine.