Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment

  • An Erratum to this article was published on 01 July 1999

Abstract

We report here that ultraviolet irradiation substantially reduced the mRNA and protein of the two major nuclear retinoid receptors, RAR-γ and RXR-α, in human skin in vivo. Pre-treatment with retinoic acid mitigated this loss of nuclear retinoid receptors. Ultraviolet irradiation caused a near-total loss of retinoic acid induction of two RAR/RXR target genes, cellular retinoic acid binding protein-II and RA 4-hydroxylase, but did not affect 1,25-dihydroxyvitamin D3 induction of the vitamin D receptor/RXR-regulated gene vitamin D 24-hydroxylase. In effect, ultraviolet irradiation causes a functional vitamin A deficiency that may have deleterious effects on skin function, contributing to skin photo-aging and carcinogenesis.

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Figure 1: Ultraviolet irradiation reduces nuclear retinoid receptor proteins and mRNAs in adult human skin in vivo.
Figure 2: Repeated exposure to UV irradiation causes sustained reduction in RXR-α, but not RAR-γ, in human skin in vivo.
Figure 3: Pre-treatment with topical RA reduces loss of RAR-γ and RXR-α in UV-irradiated adult human skin in vivo.
Figure 4: UV irradiation abolishes responsiveness to all-trans retinoic acid (RA), but not to 1,25-dihydroxyvitamin D3 in human skin in vivo.

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Acknowledgements

The authors thank C. Petersen and S. Rehbine for tissue procurement, J. Granger for technical assistance, L. VanGoor for graphics preparation, T. Hamilton for statistical analyses and A. Chapple for editorial assistance. We thank P. Chambon for RAR and RXR cDNA plasmids, M. Petkovich for human RA 4-hydroxylase cDNA, M. Haussler for human vitamin D 24-hydroxylase cDNA, and M.R. Uskokovic and P. Bollag at Hoffmann La Roche (Nutley, New Jersey) for 1,25-dihydroxyvitamin D 3 . This study was supported in part by the Babcock Endowment for Dermatological Research, the Dermatology Foundation (SK), and a grant from the Johnson & Johnson Corporation.

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Correspondence to Gary J. Fisher.

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Wang, Z., Boudjelal, M., Kang, S. et al. Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment. Nat Med 5, 418–422 (1999). https://doi.org/10.1038/7417

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