Abstract
Premature skin aging, known as photoaging, results from damage to human skin cells caused by solar ultraviolet (UV) radiation. At the macro level, the symptoms of photoaging manifest as wrinkles, mottled pigmentation, leathery texture, laxity, reduced resiliency, and sallowness. We have investigated the molecular mechanisms by which UV damages collagen in the dermal extracellular matrix. At the molecular level, photoaging results from UV induction of matrix metalloproteinases (MMPs) that degrade skin collagen. UV induction of MMPs is inhibited when skin is pretreated with all-trans retinoic acid (tRA), suggesting that tRA may prevent UV-induced collagen destruction, in addition to improving the appearance of already damaged skin. tRA prevents UV induction of c-Jun protein that is required for MMP gene expression. However, topically applied tRA does not inhibit UV-induced c-Jun kinase activity in human skin in vivo, as it does in cultured cells. It is possible that tRA inhibits UV inducted accumulation of c-Jun protein by stimulating its degradation through the ubiquitin-proteasome pathway.
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References
Rosette, C., and Karin, M., Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors., Science, 274, 1194 (1996).
Fisher, G. J., Talwar, H. S., Lin, J., Lin, P., McPhillips, F., Wang, Z. Q., Li, X., Wan, Y., Kang, S., and Voorhees, J. J., Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo, J. Clin. Invest., 101, 1432 (1998).
Angel, P., and Karin, M., Specific members of the Jun protein family regulate collagenase expression in response to various extracellular stimuli, Matrix Suppl, 1,156 (1992).
Fisher, G. J., Datta, S. C., Talwar, H. S., Wang, Z. Q., Varani, J., Kang, S., and Voorhees, J. J., Molecular basis of sun-induced premature skin ageing and retinoid antagonism., Nature, 379, 335 (1996).
Gilchrest, B. A., and Yaar, M., Aging and photaging of the skin: observations at the cellular and molecular level., Br. J. Dermatol., 127, 25 (1992).
Fisher, G. J., Wang, Z. Q., Datta, S. C., Varani, J., Kang, S., and Voorhees, J. J., Pathophysiology of premature skin aging induced by ultraviolet light., N. Engl. J. Med., 337, 1419 (1997).
Borden, P., and Heller, R. A., Transcriptional control of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases., Crit. Rev. Eukaryot. Gene Expr., 7, 159 (1997).
Chen, J. Y., Penco, S., Ostrowski, J., Balaguer, P., Pons, M., Starrett, J. E., Reczek, P., Chambon, P., and Gronemeyer, H., RAR-specific agonists/antagonists which dissociate transactivation and AP-1 transrepression, inhibit anchorage-independent cell proliferation., EMBO J., 14, 1187 (1995).
Musti, A. M., Treier, M., and Bohmann, D., Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases., Science, 275, 400 (1997).
Fisher, G. J., Talwar, H. S., Lin, J., and Voorhees, J. J., Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid, Photochem Photobiol, in press (1998).
Lee, H. Y., Walsh, G. L., Dawson, M. I., Hong, W. K., and Kurie, J. M., All-trans retinoic acid inhibits Jun N-terminal kinase-dependent signaling pathways., J. Biol. Chem., 273, 7066 (1998).
Caelles, C., Gonzalez-Sancho, J. M., and Munoz, A., Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway., Genes & Development, 11, 3351 (1997).
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Fisher, G.J., Voorhees, J.J. (1999). Molecular Pathophysiology of Photoaging in Human Skin and the Effect of All-Trans Retinoic Acid. In: Holick, M.F., Jung, E.G. (eds) Biologic Effects of Light 1998. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5051-8_33
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DOI: https://doi.org/10.1007/978-1-4615-5051-8_33
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