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 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.
Fisher
G J
GJ
Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Datta
S
S
Wang
Z
Z
Li
X Y
XY
Quan
T
T
Chung
J H
JH
Kang
S
S
Voorhees
J J
JJ
D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012867:Skin / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D044465:White People
D011347:Procollagen; D016755:Proto-Oncogene Proteins c-jun; D011837:Radiation-Protective Agents; D014212:Tretinoin