Expression and regulation of mrna coding for acidic and basic fibroblast growth factor and transforming growth factor α in cells derived from human skin

We investigated the regulation of mRNAs coding for acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and transforming growth factor-α (TGFα) in cultures of human neonatal foreskin fibroblasts, keratinocytes, and melanocytes. Each cell type was propagated in an optimized serum-free medium. In rapidly growing fibroblasts, the addition of fetal bovine serum caused a modest induction of aFGF message within 2 h in conjunction with a concomitant elevation of bFGF transcripts. In these same cells, TGFa mRNA could not be detected in any experimental condition. In contrast, keratinocytes rapidly growing in the presence of epidermal growth factor (EGF) contained transcripts for TGFa that increased substantially when these cells were treated with serum. This observation suggests that factors present in serum can elevate the levels of TGFa mRNA beyond the levels already present in keratinocyte cultures growing in the presence of EGF. These same keratinocyte cultures had low to undetectable levels of bFGF or aFGF message, and the levels of these mRNAs were not affected by serum treatment. Treatment of keratinocytes proliferating in the presence of EGF with TGFβ for 48 h caused expression of bFGF mRNA in four of six independent cell strains. TGFβ-enhanced expression of bFGF mRNA occurred as early as 12-24 h after TGFα exposure. TGFβ did not enhance the expression of mRNA for aFGF or TGFα in keratinocytes. Melanocytes failed to express detectable levels of mRNA coding for any of these growth factors in the presence or absence of TGFβ or serum. Collectively, our results demonstrate that' distinct patterns of growth factor gene expression occur in different normal cell types isolated from human skin.