Prevention of IV-induced functional vitamin A deficiency through the use of topically applied retinoid

摘要

Invention Patent: B "PREVENTION OF IV FUNCTIONAL VITAMIN DEFICIENCY THROUGH THE USE OF TOPICALLY APPLIED RETINOID" D. The vitamin A metabolite of all-trans retinoic acid (RA) is critical for normal skin function. Ultraviolet (UV) irradiation markedly reduces the mRNA and protein of the two main nuclear retinoid receptors, RAR- sym and RXR- 244 in human skin in vivo. Half the dose of UV that causes the skin to flush was enough to reduce the retinoid receptor mRNA levels. The maximum reduction of RAR- sym and RXR- 244 proteins occurs between 8 and 16 hours after UV irradiation. With multiple UV exposures, RXR- 244 remained decreased, but RAR- sym recovered to normal levels. The application of RA 24 hours before exposure to UV partially prevented the loss of nuclear retinoid receptors. UV irradiation completely prevented RA induction of two genes regulated by the retinoid receptor, cellular retinoic acid binding protein-II (CRABP-I) and RA 4-hydroxylase. In contrast, UV irradiation did not affect the induction of 1,25-dihydroxyvitamin D ~ 3 ~ of the gene regulated by the vitamin D receptor, vitamin D 24-hydroxylase, indicating that UV selectivity interferes with the signaling mode of retinoid. These data show for the first time that UV especially reduces retinoid receptor levels and drastically suppresses the expression of the retinoid-responsive gene in human skin in vivo. In reality, UV causes a deficiency of functional vitamin A that could have a detrimental effect on the functioning of the skin, contributing to skin photoaging and carcinogenesis, which can be relieved by the application of a retinoid before exposure.