Molecular basis of sun-induced premature skin ageing and retinoid antagonism

• Published in: Nature (London) Vol. 379; no. 6563; pp. 335 - 339
• Main Authors: Fisher, Gary J, Datta, Subhash C, Talwar, Harvinder S, Wang, Zeng-Quan, Varani, James, Kang, Sewon, Voorhees, John J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 25.01.1996; Nature Publishing Group
• Subjects: Adult; Aging; Biological and medical sciences; Biological effects of radiation; Collagen - metabolism; Collagen - radiation effects; DNA - metabolism; Dose-Response Relationship, Radiation; Elastin - metabolism; Elastin - radiation effects; Enzyme Induction; Fundamental and applied biological sciences. Psychology; Humans; Ionizing radiations; Irradiation; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - radiation effects; Molecular biology; NF-kappa B - metabolism; Proteins; Skin; Skin Aging - drug effects; Skin Aging - radiation effects; Time Factors; Tissues, organs and organisms biophysics; Transcription Factor AP-1 - metabolism; Tretinoin - pharmacology; Ultraviolet radiation; Ultraviolet Rays; Human; UVB radiation; Toxicity; Collagen; Elastin; Extracellular matrix; Glycoproteins; Skin; Transcription factor NFκB; Metalloproteins; Transcription factor AP1
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/379335a0

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).