Molecular basis of sun-induced premature skin ageing and retinoid antagonism.
Damage to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation, and is believed to be responsible for the wrinkled appearance of sun-exposed skin. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).
Fisher
G J
GJ
Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0528, USA.
Datta
S C
SC
Talwar
H S
HS
Wang
Z Q
ZQ
Varani
J
J
Kang
S
S
Voorhees
J J
JJ
D000328:Adult; D003094:Collagen / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004549:Elastin / Q000378:metabolism / Q000528:radiation effects*; D004790:Enzyme Induction; D006801:Humans; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014466:Ultraviolet Rays
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014212:Tretinoin; D003094:Collagen; D004247:DNA; D004549:Elastin; D008666:Metalloendopeptidases