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GROWTH, DIFFERENTIATION, AND APOPTOSIS
5 expression through CCAAT/enhancer-binding protein-
Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York
Submitted 22 April 2007 ; accepted in final form 22 June 2007
Keratinocyte growth factor (KGF) and
5
1-integrin are not expressed in normal skin but they are both highly upregulated in the migrating epidermis during wound healing. Here we report that KGF increased
5 mRNA and protein levels in epidermoid carcinoma cells and stratified bioengineered epidermis. Interestingly, KGF increased integrin
5 in the basal as well as suprabasal cell epidermal layers. Promoter studies indicated that KGF-induced integrin
5 promoter activation was dependent on the C/EBP transcription factor binding site. Accordingly, KGF induced sustained phosphorylation of C/EBP-
that was dependent on activation of ERK1/2. In addition, a dominant negative form of C/EBP-
inhibited
5 promoter activity and blocking C/EBP-
with siRNA diminished integrin
5 expression. Taken together, our data indicate that KGF increased integrin
5 expression by phosphorylating C/EBP-
. Interestingly, KGF-induced upregulation of integrin
5 was more pronounced in three-dimensional tissue analogues than in conventional two-dimensional culture suggesting that stratified epidermis may be useful in understanding the effects of growth factors in the local tissue microenvironment.
wound healing; transcription factors; epidermis; signaling pathways
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