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.
Kobayashi
T
T
Department of Dermatology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. tkobayas@derma01.m.chiba-u.ac.jp
Kishimoto
J
J
Ge
Y
Y
Jin
W
W
Hudson
D L
DL
Ouahes
N
N
Ehama
R
R
Shinkai
H
H
Burgeson
R E
RE
D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000201:enzymology* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012867:Skin / Q000166:cytology / Q000378:metabolism
D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C032253:involucrin; D007633:Keratins; D020780:Matrix Metalloproteinase 9; D002118:Calcium