Retinoic Acid Inhibits Induction of c-Jun Protein by Ultraviolet Radiation that Occurs Subsequent to Activation of Mitogen-activated Protein Kinase Pathways in Human Skin In Vivo

Human skin is exposed daily to solar ultraviolet (UV) radia-tion. UV induces the matrix metalloproteinases collagenase, 92-kD gelatinase, and stromelysin, which degrade skin con-nective tissue and may contribute to premature skin aging (photoaging). Pretreatment of skin with all-trans retinoic acid ( t RA) inhibits UV induction of matrix metalloprotein-ases. We investigated upstream signal transduction path-ways and the mechanism of t RA inhibition of UV induction of matrix metalloproteinases in human skin in vivo. Expo-sure of human skin in vivo to low doses of UV activated EGF receptors, the GTP-binding regulatory protein