Submitted on April 22, 2007
Accepted on June 22, 2007
KGF promotes integrin alpha-5 expression through CCAAT/enhancer-binding protein-beta
Piyush Koria1 and Stelios T. Andreadis1*
1 Chemical and Biological Engineering, State University of New York at Buffalo, Amherst, New York, United States
* To whom correspondence should be addressed. E-mail: sandread{at}eng.buffalo.edu.
Keratinocyte growth factor (KGF) and integrin alpha5-beta1 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.
