TGF-α and TGF-β expression during sodium-N-butyrate-induced differentiation of human keratinocytes: Evidence for subpopulation-specific up-regulation of TGF-β mRNA in suprabasal cells

Sodium-N-butyrate (NaB) induces terminal differentiation and cornified envelope formation in cultured human keratinocytes. In the present study we explored the question of whether NaB-induced maturation could be mediated through changes in TGF-α and TGF-β expression in normal keratinocytes. NaB induced a fourfold increase in TGF-β mRNA transcript levels. This increase in TGF-β mRNA abundance occurred only within the nonbasal keratinocyte subpopulation which maximally responds to NaB treatment by progression to cornified envelopes. Basal keratinocytes, which are relatively refractive to cornified envelope formation, did not show any increase in TGF-β mRNA abundance after NaB treatment. By comparison, TGF-α mRNA transcript and extracellular TGF-α protein levels were unaffected by NaB treatment. A 50% decrease in EGF receptor binding was observed in NaB-treated keratinocyte cultures, rendering the cells less responsive to proliferation induction.