Molecular Pathophysiology of Photoaging in Human Skin and the Effect of All-Trans Retinoic Acid

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 W-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.