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

• Published in: British journal of dermatology (1951) Vol. 152; no. 1; pp. 115 - 121
• Main Authors: Yano, K., Kadoya, K., Kajiya, K., Hong, Y-K., Detmar, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-01-2005; Blackwell; Oxford University Press
• Subjects: Adult; angiogenesis; Biological and medical sciences; Dermatology; Down-Regulation - radiation effects; Elastic Tissue - radiation effects; Epidermis - metabolism; Epidermis - pathology; Humans; Hyperplasia; Image Processing, Computer-Assisted - methods; Leukocytes - enzymology; Medical sciences; Middle Aged; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; neutrophil elastase; Pancreatic Elastase - biosynthesis; Radiation Injuries - etiology; Radiation Injuries - metabolism; Radiation Injuries - pathology; Reverse Transcriptase Polymerase Chain Reaction - methods; Skin - blood supply; Skin - radiation effects; Skin Aging - pathology; Thrombospondin 1 - biosynthesis; Thrombospondin 1 - genetics; thrombospondin-1; ultraviolet B; Ultraviolet Rays - adverse effects; Up-Regulation - radiation effects; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Human; Leukocyte elastase; Serine endopeptidases; Enzyme; Dermatology; UVB radiation; thrombospondm-1; Experimental study; Peptidases; Vascular endothelium growth factor; Ultraviolet irradiation; neutrophil elastase; ultraviolet B; vascular endothelial growth factor; Hydrolases; Skin; Biological effect; Thrombospondin; ongiogenesis
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2005.06368.x

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.