Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin wounds

We examined the epidermal gene expression during the proliferative phase of wound healing. Matrix metalloproteases were the group of proteases most prominently up-regulated in skin wounds, whereas serine protease inhibitors were the most strongly up-regulated protease inhibitors. Furthermore, we found down-regulation of genes involved in the extrinsic pathway of apoptosis. This together with the up-regulation of inhibitors of leukocyte serine proteases likely represents a protective step to ensure survival of keratinocytes in the inflammatory wound environment. The down-regulation of proapoptotic genes in the extrinsic pathway of apoptosis was not accompanied by a down-regulation of receptors indicating that the keratinocytes in skin wounds did not become less responsive to external stimuli. Examining the transcription factor binding sites in the promoters of the most differentially expressed genes between normal skin and skin wounds a significant overrepresentation of binding sites were found for STAT-5, SRY and members of the FOXO-family of transcription factors.