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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/C1020    most recent 00169.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koria, P. Articles by Andreadis, S. T. Search for Related Content PubMed PubMed Citation Articles by Koria, P. Articles by Andreadis, S. T.

GROWTH, DIFFERENTIATION, AND APOPTOSIS

KGF promotes integrin 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 ₅₁-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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