A novel mechanism of matrix metalloproteinase-9 gene expression implies a role for keratinization

To investigate the pathophysiological role of matrix metalloproteinase (MMP)‐9 in the skin, we analyzed MMP‐9 expression from human keratinocytes in culture. MMP‐9 and the terminal differentiation marker involucrin were co‐localized in the same keratinocytes with a high concentration of Ca 2+ , a potent stimulator of differentiation. We identified the novel KRE‐M9 element, further downstream to the previously reported TPA responsive element in the MMP‐9 promoter, and both of these two elements were shown to be important for MMP‐9 transcription and Ca 2+ induction. The concomitant upregulation of MMP‐9 and involucrin transcripts was probably due to the very similar gene regulatory elements, KRE‐M9 and KRE‐4, in their respective promoters. These results indicate a novel mechanism of transcriptional regulation for MMP‐9 in the process of keratinization, implying the probable association of apoptosis and differentiation of keratinocytes in epidermal skin tissue.