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

Gary J. Fisher, Subhash C. Datta, Harvinder S. Talwar, Zeng Quan Wang, James Varani, Sewon Kang, John J. Voorhees

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish (US)
Pages (from-to)335-339
Number of pages5
JournalNature
Volume379
Issue number6563
DOIs
StatePublished - Jan 25 1996
Externally publishedYes

ASJC Scopus subject areas

  • General

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