title: Damage to skin extracellular matrix induced by UV exposure.
abstract: CONCLUSIONS
  Chronic exposure to environmental ultraviolet radiation (UVR) plays a key role in both photocarcinogenesis and induction of accelerated skin aging. Although the spatiotemporal consequences of UVR exposure for the composition and architecture of the dermal extracellular matrix (ECM) are well characterized, the pathogenesis of photoaging remains poorly defined. Given the compelling evidence for the role of reactive oxygen species (ROS) as mediators of photoaging, UVR-exposed human skin may be an accessible model system in which to characterize the role of oxidative damage in both internal and external tissues.
  
  
  BACKGROUND
  Although the cell-mediated degradation of dermal components via UVR-induced expression of ECM proteases has long been identified as an integral part of the photoaging pathway, the relative importance and identity of cellular and extracellular photosensitizers (direct hit and bystanders models, respectively) in initiating this enzymatic activity is unclear. Recently, both age-related protein glycation and relative amino-acid composition have been identified as potential risk factors for photo-ionization and/or photo-sensitization. Here, we propose a selective multi-hit model of photoaging.
  
  
  RESULTS
  Bioinformatic analyses can be employed to identify candidate UVR targets/photosensitizers, but the action of UVR on protein structure and/or ROS production should be verified experimentally. Crucially, in the case of biochemically active ECM components such as fibronectin and fibrillin, the downstream effects of photo-degradation on tissue homeostasis remain to be confirmed.
  
  
  CONCLUSIONS
  Both topical antioxidants and inhibitors of detrimental cell signaling may be effective in abrogating the effects of specific UVR-mediated protein degradation in the dermis.
authors.affiliation: 1 The Dermatology Centre, Salford Royal Hospital, Institute of Inflammation and Repair, The University of Manchester , Manchester Academic Health Science Centre, Manchester, United Kingdom .
authors.forename: Rachel E B
authors.initials: RE
authors.lastname: Watson
authors.forename: Neil K
authors.initials: NK
authors.lastname: Gibbs
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sherratt
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species