UV radiation induces the release of angiopoietin-2 from dermal microvascular endothelial cells
Fatemeh Navid
Beiersdorf AG, 20245 Hamburg, Germany
Department of Dermatology and Allergology, University Kiel, 24105, Kiel, Germany
Search for more papers by this authorThomas Korff
Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, 69120 Heidelberg, Germany
These two authors contributed equally to this work.
Search for more papers by this authorGitta Neufang
Beiersdorf AG, 20245 Hamburg, Germany
These two authors contributed equally to this work.
Search for more papers by this authorFatemeh Navid
Beiersdorf AG, 20245 Hamburg, Germany
Department of Dermatology and Allergology, University Kiel, 24105, Kiel, Germany
Search for more papers by this authorThomas Korff
Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, 69120 Heidelberg, Germany
These two authors contributed equally to this work.
Search for more papers by this authorGitta Neufang
Beiersdorf AG, 20245 Hamburg, Germany
These two authors contributed equally to this work.
Search for more papers by this authorAbstract
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.
Supporting Information
Figure S1. Two defined areas of one forearm of volunteers were irradiated with 1.5 MED SSR while the other arm was left untreated and used as a control.
Figure S2. Linear UV spectra Oriel instrument (SSR).
| Filename | Description |
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| EXD_1416_sm_FigS1.ppt213 KB | Supporting info item |
| EXD_1416_sm_FigS2.ppt130 KB | Supporting info item |
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