PREVENTION OF UV-INDUCED FUNCTIONAL VITAMIN A DEFICIENCY THROUGH USE OF TOPICALLY APPLIED RETINOID

摘要

The vitamin A metabolite all-trans retinoic acid (RA) is critical for normal skin function. Ultraviolet irradiation (UV) markedly reduces the mRNA and protein of the two major nuclear retinoid receptors, RAR- gamma and RXR- alpha in human skin in vivo. One half the dose of UV that causes skin reddening was sufficient to reduce retinoid receptor mRNA levels. Maximal reduction of RAR- gamma and RXR- alpha proteins occurred between 8 and 16 hours after UV irradiation. With multiple exposures to UV, RXR- alpha remained decreased, but RAR- gamma recovered to normal levels. Application of RA 24 hours before UV exposure partially prevented loss of nuclear retinoid receptors. UV irradiation completely prevented RA induction of two retinoid receptor-regulated genes, cellular retinoic acid binding protein-II(CRABP-II) and RA 4-hydroxylase. In contrast, UV irradiation did not affect 1,25-dihydroxyvitamin D3 induction of the vitamin D receptor-regulated gene, vitamin 0 24-hydroxylase, indicating that UV selectively interferes with the retinoid-signaling pathway. These data demonstrate for the first time that UV specially reduces retinoid receptor levels and dramatically suppresses retinoid-responsive gene expression in human skin in vivo. In effect, UV causes a functional vitamin A deficiency that could have deleterious effects on skin function, contributing to skin photoaging and carcinogenesis, which can be ameliorated by application of a retinoid prior to exposure.