TY - JOUR
T1 - Molecular basis of sun-induced premature skin ageing and retinoid antagonism
AU - Fisher, Gary J.
AU - Datta, Subhash C.
AU - Talwar, Harvinder S.
AU - Wang, Zeng Quan
AU - Varani, James
AU - Kang, Sewon
AU - Voorhees, John J.
PY - 1996/1/25
Y1 - 1996/1/25
N2 - 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-κB, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1, 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-κB 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).
AB - 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-κB, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1, 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-κB 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).
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U2 - 10.1038/379335a0
DO - 10.1038/379335a0
M3 - Article
C2 - 8552187
AN - SCOPUS:0030069213
SN - 0028-0836
VL - 379
SP - 335
EP - 339
JO - Nature
JF - Nature
IS - 6563
ER -