Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid

Solar UV radiation damages human skin, affecting skin tone and resiliency a nd leading to premature aging (photoaging), the symptoms of which include l eathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metallo proteinases (MMP) that degrade skin collagen, We find that pretreatment of human skin with all-trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV-induced collagen destruction an d may therefore be able to lessen the effects of photoaging, The tRA preven ts UV-induced accumulation of c-Jun protein, which is required for MMP gene expression, Activation of c-Jun transcriptional activity requires N-termin al phosphorylation, The majority of c-Jun in human skin in vivo is N-termin al phosphorylated, Topically applied tRA does not inhibit N-terminal phosph orylation by UV-induced c-Jun kinase activity in human skin, The tRA likely acts to reduce UV induction of c-Jun protein by stimulating its breakdown through the ubiquitin-proteasome pathway.