Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Abstract

DAMAGE to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation1–3, and is believed to be responsible for the wrinkled appearance of sun-exposed skin4,5. 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-KB, which are known to be stimulators of metalloproteinase genes6,7. All-transretinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloprotein-ases, resulting from activation of AP-1 and NF-KB 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).

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Talwar, H. S., Griffiths, C. E. M., Fisher, G. J., Hamilton, T. A. & Voorhees, J. J. J. invest. Dermat. 105, 285–290 (1995).

    CAS  Article  Google Scholar 

  2. 2

    Lavker, R. M. J. invest. Dermat. 73, 559–566 (1979).

    Article  Google Scholar 

  3. 3

    Smith, J. G., Davidson, E. A., Sams, W. M. & Clark, R. D. J. invest. Dermat. 39, 347–350 (1962).

    CAS  Article  Google Scholar 

  4. 4

    Kligman, L. H. & Kligman, A. M. Photodermatology 3, 215–227 (1986).

    CAS  PubMed  Google Scholar 

  5. 5

    Wlaschek, M. et al. Photchem. Photobiol. 59, 550–556 (1994).

    CAS  Article  Google Scholar 

  6. 6

    Angel, P. et al. Cell 49, 729–739 (1987).

    CAS  Article  Google Scholar 

  7. 7

    Sato, H. & Seiki, M. Oncogene 8, 395–405 (1993).

    CAS  PubMed  Google Scholar 

  8. 8

    Salbert, G. et al. Molec. Endocr. 7, 1347–1356 (1993).

    CAS  PubMed  Google Scholar 

  9. 9

    Oikarinen, A., Kylmaniemi, M., Autio-Harmainen, A., Autio, P. & Salo, T. J. invest. Dermat. 101, 205–210 (1993).

    CAS  Article  Google Scholar 

  10. 10

    Saarialho-Kere, U. K., Pentland, A. P., Birkedal-Hansen, H., Parks, W. C. & Welgus, H. G. J. clin. Invest. 94, 79–88 (1994).

    CAS  Article  Google Scholar 

  11. 11

    Mauch, C., Krieg, T. & Bauer, E. A. Arch. Dermat. Res. 287, 107–114 (1994).

    CAS  Article  Google Scholar 

  12. 12

    Eisen, A. Z. J. Invest. Dermat. 52, 442–448 (1969).

    CAS  Article  Google Scholar 

  13. 13

    Devary, Y., Gottlieb, R. A., Lau, L. F. & Karin, M. Molec. cell. Biol. 11, 2804–2811 (1991).

    CAS  Article  Google Scholar 

  14. 14

    Angel, P. & Karin, M. Matrix Suppl. 1, 156–164 (1992).

    CAS  PubMed  Google Scholar 

  15. 15

    Quinones, S., Buttice, G. & Kurkinen, M. Biochem. J. 302, 471–477 (1994).

    CAS  Article  Google Scholar 

  16. 16

    Frisch, S. M. & Morisaki, J. H. Molec. cell. Biol. 10, 6524–6532 (1990).

    CAS  Article  Google Scholar 

  17. 17

    Nicholson, R. C. et al. EMBO J. 9, 4443–4454 (1990).

    CAS  Article  Google Scholar 

  18. 18

    Yang-Yen, H. F. et al. Cell 62, 1205–1215 (1990).

    CAS  Article  Google Scholar 

  19. 19

    Schule, R. et al. Cell 62, 1217–1226 (1990).

    CAS  Article  Google Scholar 

  20. 20

    Pfahl, M. Endocr. Rev. 5, 651–658 (1993).

    Google Scholar 

  21. 21

    Fisher, G. J. et al. J. biol. Chem. 269, 20629–20635 (1994).

    CAS  PubMed  Google Scholar 

  22. 22

    Weinstein, G. D. & Boucek, R. J. J. invest. Dermat. 35, 227–229 (1960).

    CAS  Article  Google Scholar 

  23. 23

    Bailly, B. S. et al. J. invest. Dermat. 94, 47–51 (1990).

    CAS  Article  Google Scholar 

  24. 24

    Rafal, E. S. et al. New. Engl. J. Med. 326, 368–374 (1992).

    CAS  Article  Google Scholar 

  25. 25

    Hill, P. A. et al. Biochem. J. 308, 167–175 (1995).

    CAS  Article  Google Scholar 

  26. 26

    Fisher, G. J. et al. J. invest. Dermat. 96, 699–707 (1991).

    CAS  Article  Google Scholar 

  27. 27

    Hu, C. L., Crombie, G. & Franzblau, C. Analyt. Biochem. 88, 638–643 (1978).

    CAS  Article  Google Scholar 

  28. 28

    Hibbs, M. S., Hasty, K. A., Seyer, J. M., Kang, A. H. & Mainardi, C. L. J. biol. Chem. 260, 2493–2500 (1985).

    CAS  PubMed  Google Scholar 

  29. 29

    Werb, Z., Tremble, P. M., Behrendtsen, O., Crowley, E. & Damsky, C. H. J. Cell Biol. 109, 877–889 (1989).

    CAS  Article  Google Scholar 

  30. 30

    Murphy, G. et al. Biochem. J. 258, 463–472 (1989).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fisher, G., Datta, S., Talwar, H. et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379, 335–339 (1996). https://doi.org/10.1038/379335a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing