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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
Author(s) -
Yano K.,
Kadoya K.,
Kajiya K.,
Hong YK.,
Detmar M.
Publication year - 2005
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2005.06368.x
Subject(s) - angiogenesis , downregulation and upregulation , thrombospondin 1 , vascular endothelial growth factor , cd31 , hacat , neovascularization , keratinocyte , vascular endothelial growth factor a , cancer research , pathology , chemistry , biology , immunology , medicine , in vitro , vegf receptors , biochemistry , gene
Summary 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. Objectives 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.