Multi-stage program of differentiation in human epidermal keratinocytes: regulation by retinoids.

The proliferation and differentiation of epidermal keratinocytes in vivo and in vitro is influenced by a variety of different factors, including several peptide growth factors, protein kinase C activators, retinoids, and various cytokines. Retinoids can affect the proliferation of human epidermal keratinocytes either positively or negatively and influence the multi-step program of differentiation in epidermal keratinocytes at very specific stages. Epidermal keratinocytes express nuclear retinoic acid receptors, RARalpha, and RARgamma. It is likely that at least some of the alterations in gene expression induced by retinoids are mediated through these RAR. The cytosolic retinoic acid-binding protein (CRABP), which is differentially expressed during squamous differentiation of human epidermal keratinocytes, may control the effective concentration of retinoic acid in the cell and therefore regulate indirectly gene expression.