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 and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metallo...

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Bibliographic Details
Published in:Photochemistry and photobiology 1999-02, Vol.69 (2), p.154-157
Main Authors: Fisher, G.J, Talwar, H.S, Lin, J, Voorhees, J.J
Format: Article
Language:English
Subjects:
Adult
aging
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Humans
Keratolytic Agents - therapeutic use
Metalloendopeptidases - metabolism
prevention
Proto-Oncogene Proteins c-jun - metabolism
retinoic acid
Signal Transduction
skin
Skin - enzymology
Skin - pathology
Skin - radiation effects
Skin Aging - drug effects
Transcription Factor AP-1 - metabolism
Tretinoin - therapeutic use
ultraviolet radiation
Ultraviolet Rays
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Summary:Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (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 and may therefore be able to lessen the effects of photoaging. The tRA prevents UV-induced accumulation of c-Jun protein, which is required for MMP gene expression. Activation of c-Jun transcriptional activity requires N-terminal phosphorylation. The majority of c-Jun in human skin in vivo is N-terminal phosphorylated. Topically applied tRA does not inhibit N-terminal phosphorylation 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.
ISSN:0031-8655
1751-1097
DOI:10.1111/j.1751-1097.1999.tb03268.x