MOLECULAR-BASIS OF SUN-INDUCED PREMATURE SKIN AGING AND RETINOID ANTAGONISM

DAMAGE to skin collagen and elastin (extracellular matrix) is the hall mark of long-term exposure to solar ultraviolet irradiation(1-3), and is believed to be responsible for the wrinkled appearance of sun-expos ed skin(4,5). We report here that matrix-degrading metalloproteinase m essenger RNAs, proteins and activities are induced in human skin in vi vo within hours of exposure to ultraviolet-B irradiation (UVB). Induct ion 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 a re known to be stimulators of metalloproteinase genes(6,7). All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irra diation with UVB, substantially reduced AP-1 and metalloproteinase ind uction, We propose that elevated metalloproteinases, resulting from ac tivation of AP-1 and NF-kappa B by low dose solar irradiation, degrade collagen and elastin in skin, Such damage, if imperfectly repaired wo uld result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin agei ng (photoageing).