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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 irradiation1–3, and is believed to be responsible for the wrinkled appearance of sun-exposed skin4,5. 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-KB, which are known to be stimulators of metalloproteinase genes6,7. All-transretinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloprotein-ases, resulting from activation of AP-1 and NF-KB 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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Fisher, G., Datta, S., Talwar, H. et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379, 335–339 (1996).

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