COLLAGENASE EXPRESSION IS RAPIDLY INDUCED IN WOUND-EDGE KERATINOCYTESAFTER ACUTE INJURY IN HUMAN SKIN, PERSISTS DURING HEALING, AND STOPS AT REEPITHILIALIZATION

Collagenolytic activity has been reported previously in association wi th wounds. We used in situ hybridization and immunohistochemistry to l ocalize cellular sites of interstitial collagenase production in acute wounds in human skin at days 1, 2, 4, 6, 9, and 14 after wounding. In vivo, collagenase expression peaked in migrating basal keratinocytes at the wound edge at day 1, then gradually decreased and was undetecta ble at day 9 when healing was complete. To minimize the effects of cru st formation and inflammation, we examined the healing of wounds made with a 3-mm punch in organ-cultured skin. In these in vitro wounds, re -epithelialization occurred by 5-7 d in 10% serum, although remodeling of the connective tissue was minimal. Collagenase expression showed a similar pattern as in the in vivo wounds; it was detected in migratin g keratinocytes already 4-6 h after wounding, peaked at 12-24 h, gradu ally decreased during the next few days, and subsided upon re-epitheli alization. In dermal fibroblasts, on the other hand, expression of col lagenase started considerably later, after 5-7 d in culture, and persi sted after complete re-epithelialization, indicating that collagenase is differentially regulated in different cell types. Our findings also show that collagenase induction in keratinocytes does not require inf lammation and occurs as a rapid response to wounding, suggesting that interstitial collagenase is not only necessary for remodeling of the e xtracellular matrix, but may also have a role in initiating migration of keratinocytes in wound healing.