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

Nature. 1996 Jan 25;379(6563):335-9. 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).

MeSH terms

  • Adult
  • Collagen / metabolism
  • Collagen / radiation effects*
  • DNA / metabolism
  • Dose-Response Relationship, Radiation
  • Elastin / metabolism
  • Elastin / radiation effects*
  • Enzyme Induction
  • Humans
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / radiation effects*
  • NF-kappa B / metabolism
  • Skin Aging / drug effects
  • Skin Aging / radiation effects*
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Tretinoin / pharmacology*
  • Ultraviolet Rays*


  • NF-kappa B
  • Transcription Factor AP-1
  • Tretinoin
  • Collagen
  • DNA
  • Elastin
  • Metalloendopeptidases