Gap-junctional protein connexin 43 is expressed in dermis and epidermis of human skin: differential modulation by retinoids.
Retinoids are effective modulators of proliferation and differentiation of keratinocytes in vivo and in vitro. In mouse 10T1/2 cells, retinoid action on proliferation and neoplastic transformation is correlated with the upregulation of gap-junctional communication and expression of connexin 43 (Cx43). In the present study we have determined if retinoids induce similar effects on gene expression in human skin. Studies were conducted in intact skin and on cultured keratinocytes and dermal fibroblasts. In a clinical study, 2 weeks of treatment with 0.05% all-trans retinoic acid resulted in increased expression of Cx43 mRNA and protein in epidermis. Expression occurred predominantly in the suprabasal layer. Cultured cells exhibited a differential response to retinoic acid. In keratinocytes, increased expression of Cx43 occurred at low (10(-11) M) concentrations, whereas inhibition occurred at high (10(-7) M) concentrations; however, junctional communication, measured by dye transfer, was not altered over this concentration range. Dermal fibroblasts, in contrast, exhibited a dose-dependent increased expression of Cx43 at concentrations up to 10(-7) M retinoic acid and proportionately increased their junctional communication over this dose range. These data indicate that control of Cx43 gene expression by retinoids in human skin cells is complex. The production of gradients of junctional channels could play a role in the control of growth and differentiation in epidermis.