Retinoic acid receptor expression in human skin keratinocytes and dermal fibroblasts in vitro

ABSTRACT Retinoic acid is essential for the normal differentiation of epithelia but its cellular function is obscure. The expression patterns of retinoic acid receptors (RARs) in skin cell types may give an insight into the role of retinoic acid in skin. We have compared the patterns of RAR expression in human keratinocytes and dermal fibroblasts in vitro, and studied the effects of retinoic acid on RAR expression. RAR-α and RAR-γ were expressed in keratinocytes and fibroblasts: RAR-γ was expressed at similar levels in both cell types but RAR-α was more abundant in fibroblasts. There were no differences in expression of either RAR-α or RAR-γ between stratifying (high-calcium medium) and proliferating (low-calcium medium) keratinocytes and expression of these RARs was unaffected by retinoic acid. RAR-β was undetectable in keratinocytes. In the majority of fibroblast cell lines, RAR-β transcripts were either undetectable or expressed at a low level. Retinoic acid at low concentrations (10−10 to 10−9 M) rapidly induced the expression of RAR-γ. Cyclic adenosine monophosphate (cAMP) analogues inhibit RAR-β induction in teratocarcinoma cells. However, dibutyryl-cAMP did not affect RAR-β induction in fibroblasts. Forskolin, an adenylate cyclase activator, and the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) decreased constitutive RAR-β mRNA levels but did not block induction of RAR-β by retinoic acid. Since intracellular cAMP levels were only increased detectably in response to forskolin, the reduction in constitutive levels of RAR-β mRNA may be mediated by mechanisms other than via cAMP.