UV-light-induced signal cascades and skin aging.
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 regulate expression of multiple genes. These signaling pathways converge to stimulate transcription factor 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)-beta 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-beta 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.
Rittié
Laure
L
Department of Dermatology, University of Michigan, 1150 West Medical Center Drive, R6447 Medical Science I, Ann Arbor, MI 48109-0609, USA.
Fisher
Gary J
GJ
D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects*; D015595:Skin Aging / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D014466:Ultraviolet Rays