title: UV radiation induces the release of angiopoietin-2 from dermal microvascular endothelial cells.
abstract: In human skin, ultraviolet radiation (UVR)-induced erythema is characterized by the inflammatory and angiogenic activation of dermal endothelial cells. Recently, it has been shown that the release of angiopoietin-2 (Ang-2) from cytoplasmic storages of activated endothelial cells is crucial for the induction of inflammation and angiogenesis. Therefore, we hypothesized that UVR exposure induces the release of Ang-2 from endothelial cells controlling the early steps of erythema formation. In an in vivo study, suction blister fluids generated from UV-irradiated skin showed significantly increased concentrations of Ang-2, vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNFα). Likewise, in vitro UVR exposure of human dermal microvascular endothelial cells (HDMECs) triggered the release of Ang-2 that enhanced the pro-inflammatory response of these cells and facilitated their detachment from smooth muscle cells as evidenced by employing a three-dimensional co-culture spheroid model. These effects were inhibited by angiopoietin-1 (Ang-1), which competes with Ang-2 for binding the endothelial cell Tie2 receptor. Collectively, these observations suggest that UVR triggers the release of endothelial Ang-2 which may promote the destabilization and pro-inflammatory phenotype of the microvascular endothelium. As Ang-1 counteracts UVR-induced effects, stimulating the Ang-1 activity may represent a strategy to stabilize the dermal microcirculatory system, thus protecting against UVR-induced skin damages.
authors.affiliation: Beiersdorf AG, 20245 Hamburg, Germany.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Navid
authors.forename: Ludger
authors.initials: L
authors.lastname: Kolbe
authors.forename: Franz
authors.initials: F
authors.lastname: Stäb
authors.forename: Thomas
authors.initials: T
authors.lastname: Korff
authors.forename: Gitta
authors.initials: G
authors.lastname: Neufang
mesh_terms: D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000494:pharmacology; D042702:Angiopoietin-2 / Q000378:metabolism* / Q000494:pharmacology; D001768:Blister / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D018920:Coculture Techniques; D020405:Dermis / Q000098:blood supply / Q000166:cytology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014466:Ultraviolet Rays; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020302:Weibel-Palade Bodies / Q000378:metabolism / Q000528:radiation effects; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D013755:Tetradecanoylphorbol Acetate