title: Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin-1.
abstract: BACKGROUND
  We have previously demonstrated that skin-specific overexpression of the endogenous angiogenesis inhibitor thrombospondin (TSP)-1 prevented chronic ultraviolet (UV) B-induced angiogenesis, inflammatory cell infiltration and cutaneous photodamage in mice.
  
  
  OBJECTIVE
  To elucidate the mechanisms by which acute UVB-induced angiogenesis induces dermal damage, and to study the molecular regulation of acute UVB-induced angiogenesis in human skin.
  
  
  METHODS
  We subjected five healthy volunteers to acute UVB irradiation (2 minimal erythema doses) and performed histological analysis at 48 h after UVB irradiation.
  
  
  RESULTS
  Histology revealed epidermal hyperplasia, infiltration of elastase-producing neutrophils and elastin fibre damage. Immunohistochemistry for CD31 demonstrated pronounced angiogenesis with a significant increase in both vascular density and vessel size, associated with increased endothelial cell proliferation. Whereas constitutive expression of TSP-1 but only weak expression of vascular endothelial growth factor (VEGF) were detected in normal human epidermis, pronounced downregulation of TSP-1 and upregulation of VEGF were observed in epidermal keratinocytes after acute UVB irradiation. These findings were confirmed by quantitative reverse transcription-polymerase chain reaction analysis after UVB irradiation of cultured HaCaT keratinocytes in vitro.
  
  
  CONCLUSIONS
  Together, these data indicate that a disruption of the balance between VEGF and TSP-1 expression leads to a UVB-induced angiogenic switch, facilitating the infiltration of elastase-producing leucocytes and cutaneous photodamage.
authors.affiliation: Shiseido Life Science Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama, Kanagawa-ken 224-8558, Japan. kiichiro.yano@to.shiseido.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Kadoya
authors.forename: K
authors.initials: K
authors.lastname: Kajiya
authors.forename: Y-K
authors.initials: YK
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Detmar
mesh_terms: D000328:Adult; D015536:Down-Regulation / Q000528:radiation effects; D004547:Elastic Tissue / Q000528:radiation effects; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007962:Leukocytes / Q000201:enzymology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010196:Pancreatic Elastase / Q000096:biosynthesis; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000098:blood supply* / Q000528:radiation effects; D015595:Skin Aging / Q000473:pathology; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation / Q000528:radiation effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D010196:Pancreatic Elastase