c-Jun–dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid
Gary J. Fisher, … , Sewon Kang, John J. Voorhees
Gary J. Fisher, … , Sewon Kang, John J. Voorhees
Published September 1, 2000
Citation Information: J Clin Invest. 2000;106(5):663-670. https://doi.org/10.1172/JCI9362.
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Article

c-Jun–dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid

Abstract

The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by UV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.

Authors

Gary J. Fisher, Subhash Datta, ZengQuan Wang, Xiao-Yan Li, Taihao Quan, Jin Ho Chung, Sewon Kang, John J. Voorhees

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All-trans retinoic acid (RA) protects against UV-induced reduction of ty...
All-trans retinoic acid (RA) protects against UV-induced reduction of type I and type III procollagen mRNA expression in human skin in vivo. Human skin was pretreated with vehicle and 0.1% RA for 24 hours, then irradiated with UV (2 MED). Skin was obtained 24 hours after UV exposure. Type I (a–d) and type III (e–h) procollagen mRNA expression was determined by digoxigenin riboprobe in situ hybridization. a and e, vehicle-treated skin; b and f, RA-treated skin; c and g, vehicle-pretreated, UV-irradiated skin; d and h, RA-pretreated, UV-irradiated skin. Insets show enlargement of cells in the dermis. Solid black lines demarcate border between epidermis and connective tissue. Areas outlined in black are shown in 2.5-fold enlargements. Data displayed are representative of six subjects. Scale bar = 10 μm.