title: Low-dose ultraviolet radiation selectively degrades chromophore-rich extracellular matrix components.
abstract: Photoageing of human skin due to chronic exposure to ultraviolet radiation (UVR) is characterized histologically by extensive remodelling of the dermal elastic fibre system. Whilst enzymatic pathways are thought to play a major role in mediating extracellular matrix (ECM) degeneration in UV-exposed skin, the substrate specificity of UVR-up-regulated and activated matrix metalloproteinases (MMPs) is low. It is unclear, therefore, how such cell-mediated mechanisms alone could be responsible for the reported selective degradation of elastic fibre components such as fibrillin-1 and fibulin-5 during the early stages of photoageing. Here we use atomic force microscopy (AFM) and scanning transmission electron microscopy (STEM) to demonstrate that physiologically attainable doses (20-100 mJ/cm(2)) of direct UV-B radiation can induce profound, dose-dependent, changes in the structure of, and mass distribution within, isolated fibrillin microfibrils. Furthermore, using reducing and native PAGE in combination with AFM, we show that, whilst exposure to low-dose UV-B radiation significantly alters the macromolecular and quaternary structures of both UV chromophore (Cys, His, Phe, Trp and Tyr)-rich fibrillin microfibrils (fibrillin-1, 21.0%) and fibronectin dimers (fibronectin, 12.9%), similar doses have no detectable effect on UV chromophore-poor type I collagen monomers (2.2%). Analysis of the published primary amino acid sequences of 49 dermal ECM components demonstrates that most elastic fibre-associated proteins, but crucially neither elastin nor members of the collagen family, are rich in UV chromophores. We suggest, therefore, that the amino acid composition of elastic fibre-associated proteins [including the fibrillins, fibulins, latent TGFbeta binding proteins (LTBPs) and the lysyl oxidase family of enzymes (LOK/LOXLs)] may predispose them to direct degradation by UVR. As a consequence, this selective acellular photochemical pathway may play an important role in initiating and/or exacerbating cell-mediated ECM remodelling in UVR-exposed skin.
authors.affiliation: Regenerative Biomedicine, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. michael.j.sherratt@manchester.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sherratt
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Bayley
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Reilly
authors.forename: Neil K
authors.initials: NK
authors.lastname: Gibbs
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Rachel E B
authors.initials: RE
authors.lastname: Watson
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004307:Dose-Response Relationship, Radiation; D004547:Elastic Tissue / Q000528:radiation effects; D005109:Extracellular Matrix / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins / Q000737:chemistry / Q000528:radiation effects; D006801:Humans; D008297:Male; D020894:Microfibrils / Q000528:radiation effects / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000528:radiation effects; D008855:Microscopy, Electron, Scanning; D015595:Skin Aging / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays; D055815:Young Adult; D054392:Adipokines
chemical_list: D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines