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Letters to Nature
Nature 379, 335 - 339 (25 January 1996); doi:10.1038/379335a0

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

Departments of Dermatology and *Pathology, University of Michigan Medical School, Kresge 1, R6558, Ann Arbor, Michigan 48109–0528, USA

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).

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References

1. Talwar, H. S., Griffiths, C. E. M., Fisher, G. J., Hamilton, T. A. & Voorhees, J. J. J. invest. Dermat. 105, 285−290 (1995). | ChemPort |
2. Lavker, R. M. J. invest. Dermat. 73, 559−566 (1979).
3. Smith, J. G., Davidson, E. A., Sams, W. M. & Clark, R. D. J. invest. Dermat. 39, 347−350 (1962). | ChemPort |
4. Kligman, L. H. & Kligman, A. M. Photodermatology 3, 215−227 (1986). | PubMed | ISI | ChemPort |
5. Wlaschek, M. et al. Photchem. Photobiol. 59, 550−556 (1994). | ChemPort |
6. Angel, P. et al. Cell 49, 729−739 (1987). | Article | PubMed | ISI | ChemPort |
7. Sato, H. & Seiki, M. Oncogene 8, 395−405 (1993). | PubMed | ISI | ChemPort |
8. Salbert, G. et al. Molec. Endocr. 7, 1347−1356 (1993). | PubMed | ChemPort |
9. Oikarinen, A., Kylmaniemi, M., Autio-Harmainen, A., Autio, P. & Salo, T. J. invest. Dermat. 101, 205−210 (1993). | ChemPort |
10. Saarialho-Kere, U. K., Pentland, A. P., Birkedal-Hansen, H., Parks, W. C. & Welgus, H. G. J. clin. Invest. 94, 79−88 (1994). | PubMed | ChemPort |
11. Mauch, C., Krieg, T. & Bauer, E. A. Arch. Dermat. Res. 287, 107−114 (1994). | ChemPort |
12. Eisen, A. Z. J. Invest. Dermat. 52, 442−448 (1969). | ChemPort |
13. Devary, Y., Gottlieb, R. A., Lau, L. F. & Karin, M. Molec. cell. Biol. 11, 2804−2811 (1991). | PubMed | ChemPort |
14. Angel, P. & Karin, M. Matrix Suppl. 1, 156−164 (1992). | PubMed | ChemPort |
15. Quinones, S., Buttice, G. & Kurkinen, M. Biochem. J. 302, 471−477 (1994). | PubMed | ChemPort |
16. Frisch, S. M. & Morisaki, J. H. Molec. cell. Biol. 10, 6524−6532 (1990). | PubMed | ChemPort |
17. Nicholson, R. C. et al. EMBO J. 9, 4443−4454 (1990). | PubMed | ISI | ChemPort |
18. Yang-Yen, H. F. et al. Cell 62, 1205−1215 (1990). | Article | PubMed | ChemPort |
19. Schule, R. et al. Cell 62, 1217−1226 (1990). | Article | PubMed | ISI | ChemPort |
20. Pfahl, M. Endocr. Rev. 5, 651−658 (1993). | Article |
21. Fisher, G. J. et al. J. biol. Chem. 269, 20629−20635 (1994). | PubMed | ISI | ChemPort |
22. Weinstein, G. D. & Boucek, R. J. J. invest. Dermat. 35, 227−229 (1960). | ChemPort |
23. Bailly, B. S. et al. J. invest. Dermat. 94, 47−51 (1990).
24. Rafal, E. S. et al. New. Engl. J. Med. 326, 368−374 (1992). | PubMed | ChemPort |
25. Hill, P. A. et al. Biochem. J. 308, 167−175 (1995). | PubMed | ChemPort |
26. Fisher, G. J. et al. J. invest. Dermat. 96, 699−707 (1991). | ChemPort |
27. Hu, C. L., Crombie, G. & Franzblau, C. Analyt. Biochem. 88, 638−643 (1978). | PubMed | ChemPort |
28. Hibbs, M. S., Hasty, K. A., Seyer, J. M., Kang, A. H. & Mainardi, C. L. J. biol. Chem. 260, 2493−2500 (1985). | PubMed | ChemPort |
29. Werb, Z., Tremble, P. M., Behrendtsen, O., Crowley, E. & Damsky, C. H. J. Cell Biol. 109, 877−889 (1989). | Article | PubMed | ISI | ChemPort |
30. Murphy, G. et al. Biochem. J. 258, 463−472 (1989). | PubMed | ChemPort |



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