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Am J Physiol Cell Physiol 293: C1020-C1031, 2007. First published June 27, 2007; doi:10.1152/ajpcell.00169.2007
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GROWTH, DIFFERENTIATION, AND APOPTOSIS

KGF promotes integrin {alpha}5 expression through CCAAT/enhancer-binding protein-beta

Piyush Koria and Stelios T. Andreadis

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 {alpha}5beta1-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 {alpha}5 mRNA and protein levels in epidermoid carcinoma cells and stratified bioengineered epidermis. Interestingly, KGF increased integrin {alpha}5 in the basal as well as suprabasal cell epidermal layers. Promoter studies indicated that KGF-induced integrin {alpha}5 promoter activation was dependent on the C/EBP transcription factor binding site. Accordingly, KGF induced sustained phosphorylation of C/EBP-beta that was dependent on activation of ERK1/2. In addition, a dominant negative form of C/EBP-beta inhibited {alpha}5 promoter activity and blocking C/EBP-beta with siRNA diminished integrin {alpha}5 expression. Taken together, our data indicate that KGF increased integrin {alpha}5 expression by phosphorylating C/EBP-beta. Interestingly, KGF-induced upregulation of integrin {alpha}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



Address for reprint requests and other correspondence: S. T. Andreadis, Bioengineering Laboratory, Dept. of Chemical and Biological Engineering, 908 Furnas Hall, Univ. at Buffalo, State Univ. of New York, Amherst, NY 14260 (e-mail: sandread{at}eng.buffalo.edu)







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