Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds.

U K Saarialho-Kere; A P Pentland; H Birkedal-Hansen; W C Parks; H G Welgus

doi:10.1172/JCI117351

Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds.

U K Saarialho-Kere, A P Pentland, H Birkedal-Hansen, W C Parks, and H G Welgus

Published July 1, 1994 - More info

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Abstract

Wound repair involves cell migration and tissue remodeling, and these ordered and regulated processes are facilitated by matrix-degrading proteases. We reported that interstitial collagenase is invariantly expressed by basal keratinocytes at the migrating front of healing epidermis (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 substrate specificity of collagenase, principally for interstitial fibrillar collagens, 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 metalloproteinases, and both can degrade many noncollagenous connective tissue macromolecules. Using in situ hybridization and immunohistochemistry, we found that both stromelysins are produced by distinct populations of keratinocytes in a variety of chronic ulcers. Stromelysin-1 mRNA and protein 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 keratinocytes at the migrating front, in the same epidermal cell population that expresses collagenase. Stromelysin-1-producing keratinocytes resided on the basement membrane, whereas stromelysin-2-producing keratinocytes were in contact with the dermal matrix. Furthermore, stromelysin-1 expression was prominent in dermal fibroblasts, whereas no signal for stromelysin-2 was seen in any dermal cell. These findings demonstrate 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.

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