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

Takashi Kobayashi, Jiro Kishimoto, Yimin Ge, William Jin, David L. Hudson, Nadia Ouahes, Ritsuko Ehama, Hiroshi Shinkai, Robert E. Burgeson

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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 Ca2+, 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 element were shown to be important for MMP-9 transcription and Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)604-608
Number of pages5
JournalEMBO Reports
Issue number7
StatePublished - 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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