DISTINCT POPULATIONS OF BASAL KERATINOCYTES EXPRESS STROMELYSIN-1 ANDSTROMELYSIN-2 IN CHRONIC WOUNDS

Wound repair involves cell migration and tissue remodeling, and these ordered and regulated processes are facilitated by matrix-degrading pr oteases. We reported that interstitial collagenase is invariantly expr essed by basal keratinocytes at the migrating front of healing epiderm is (Saarialho-Kere, U. K., E. S. Chang, H. G. Welgus, and W. C. Parks. 1992. J. Clin. Invest. 90:1952-1957). Because of the limited substrat e specificity of collagenase, principally for interstitial fibrillar c ollagens, other enzymes must also be produced in the wound environment to effectively restructure tissues with a complex matrix composition. Stromelysins-1 and -2 are closely related, yet distinct metalloprotei nases, and both can degrade many noncollagenous connective tissue macr omolecules. Using in situ hybridization and immunohistochemistry, we f ound that both stromelysins are produced by distinct populations of ke ratinocytes in a variety of chronic ulcers. Stromelysin-1 mRNA and pro tein were detected in basal keratinocytes adjacent to but distal from the wound edge in what probably represents the sites of proliferating epidermis, In contrast, stromelysin-2 mRNA was seen only in basal kera tinocytes at the migrating front, in the same epidermal cell populatio n that expresses collagenase. Stromelysin-1-producing keratinocytes re sided on the basement membrane, whereas stromelysin-2-producing kerati nocytes were in contact with the dermal matrix. Furthermore, stromelys in-1 expression was prominent in dermal fibroblasts, whereas no signal for stromelysin-2 was seen in any dermal cell. These findings demonst rate that stromelysins-1 and -2 are produced by different populations of basal keratinocytes in response to wounding and suggest that these two matrix metalloproteinases serve distinct roles in tissue repair.