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(1-3), and is believed to be responsible for the wrinkled appearance of sun-exposed skin(4,5). 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-kappa B, which are known to be stimulators of metalloproteinase genes(6,7). 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).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62525/1/379335a0.pd