REGULATION OF THE EXPRESSION OF STROMELYSIN-2 BY GROWTH-FACTORS IN KERATINOCYTES - IMPLICATIONS FOR NORMAL AND IMPAIRED WOUND-HEALING

Keratinocyte growth factor (KGF) has been implicated in wound re-epith elialization and branching morphogenesis of several organs. To determi ne whether KGF induces these effects via induction of matrix metallopr oteinase expression we have analysed the effect of KGF on the expressi on of stromelysin-2 in cultured HaCaT keratinocytes. Here we show a st rong induction of stromelysin-2 mRNA within 5-8 h of stimulation of th ese cells with KGF. The degree of induction was similar to that achiev ed by treatment with epidermal growth factor or tumour necrosis factor alpha, whereas the stimulatory effect of transforming growth factor b eta(1) was even stronger. To determine whether the induction of strome lysin-2 expression by growth factors and cytokines might be important for wound healing, we analysed the expression of this gene during the healing process of full-thickness excisional wounds in mice. Whereas s tromelysin-2 mRNA could hardly be detected in unwounded skin, a biphas ic induction was seen after injury and highest levels were found at da ys 1 and 5 after wounding. Hybridization in situ revealed the presence of stromelysin-2 mRNA in basal keratinocytes at the wound edge but no t in the underlying mesenchymal tissue. During impaired wound healing as seen in glucocorticoid-treated mice, stromelysin-2 expression was s ignificantly increased compared with untreated control mice. Taken tog ether, these results suggest that correct regulation of this broad-spe ctrum metalloproteinase might be important for normal repair.