CD 2394, a novel synthetic retinoid, initiates an embryonic type of differentiation in hyperproliferative skin

In human skin, there are 2 types of epidermal differentiation: normal differentiation, characterized by keratin 10 expression, and alternative differentiation. Alternative differentiation may be regeneration-associated differentiation (keratin 6 and 16) or re-induction of embryonic differentiation (expression of keratin 13, 15 and 19). The purpose of this study was to investigate the effect of the novel synthetic retinoid CD 2394 on hyperproliferative human skin, with respect to embryonic differentiation in particular. The effects of CD 2394 were compared with untreated and vehicle-treated skin 48 h after tape-stripping. In a multiparameter flow cytometric assay, parameters of proliferation, normal differentiation, embryonic differentiation and inflammation were assessed. With respect to proliferation, treatment with CD 2394 resulted in a decreased number of cells in the G2M-phase. Normal differentiation was decreased in CD 2394 treated skin. Furthermore, most of the CD 2394 treated samples showed expression of keratin 13, which was not seen in the otherwise treated skin. A correlation between keratin 10 and keratin 13 expression could not be demonstrated. This study showed that CD 2394 is capable of inducing an embryonic pathway of differentiation, which is distinct from normal differentiation or regeneration-associated differentiation.