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UV-light-induced signal cascades and skin aging.pdf

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UV-light-induced signal cascades and skin aging

Ageing Research Reviews 1 (2002) 705–720 Review UV-light-induced signal cascades and skin aging Laure Rittié, Gary J. Fisher ? Department of Dermatology, University of Michigan, 1150 West Medical Center Drive, R6447 Medical Science I, Ann Arbor, MI 48109-0609, USA Received 10 May 2002; accepted 10 May 2002 Abstract UV irradiation acts as a broad activator of cell surface growth factor and cytokine receptors. This ligand-independent receptor activation induces multiple downstream signaling pathways that regu- late expression of multiple genes. These signaling pathways converge to stimulate transcription fac- tor AP-1. Among genes whose expression is regulated by AP-1 are several matrix-metalloproteinase (MMP) family members and type I procollagen. UV-enhanced matrix degradation is accompanied with decreased collagen production mediated not only by activation of AP-1, but also by inhibition of transforming growth factor (TGF)- signaling. Several alterations to skin connective tissue that occur during aging are mediated by mechanisms that are similar to those that occur in response to UV irradiation. Thus, skin aging is associated with increased AP-1 activity, increased MMP expression, impaired TGF- signaling, enhanced collagen degradation, and decreased collagen synthesis. Knowledge gained from examining molecular responses of human skin to UV irradiation provides not only a framework for understanding mechanisms involved in skin aging, but also may help in development of new clinical strategies to impede chronological and UV-induced skin aging. ? 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: UV irradiation; AP-1 transcription factors; TGF- signaling; MMP expression; Type I collagen synthesis 1. Introduction As life expectancy increases in developed countries, the impact of aging on the function and appearance of skin is receiving growing interest. Skin aging is influenced by several factors, including genetics, environmental exposure (ultraviol