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

The aged appearance of skin following repeated exposure to solar ultraviole t (UV) irradiation stems largely from damage to cutaneous connective tissue , which is composed primarily of type I and type III collagens. We report h ere that a single exposure to UV irradiation causes significant loss of pro collagen synthesis in human skin. Expression of type I and type III procoll agens 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 pro collagen 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 IV irradiation and interferes with procollagen transcr iption. Pretreatment of human skin in vivo with all-trans retinoic acid inh ibits UV induction of c-Jun and protects skin against loss of procollagen s ynthesis. We have reported previously that UV irradiation induces matrix-de grading 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 procoll agen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard p remature skin aging.