Activation of the VEGFR-3 Pathway by VEGF-C Attenuates UVB-Induced Edema Formation and Skin Inflammation by Promoting Lymphangiogenesis
- Journal Article
We have previously demonstrated that UVB irradiation resulted in impaired function of cutaneous lymphatic vessels, suggesting a crucial role of lymphatic function in the mediation of UVB-induced inflammation. Nonetheless, the molecular mechanisms of lymphatic involvement in inflammation have remained unclear. Here, we show that vascular endothelial growth factor (VEGF)-C expression is downregulated after UVB irradiation, associated with enlargement of lymphatic vessels and with an increase of macrophage infiltration in the dermis. To determine whether activation of VEGF-C/VEGFR-3 signaling might reduce UVB-induced inflammation, mice were exposed to a single dose of UVB irradiation together with intradermal injection of mutant VEGF-C (Cys156Ser), which specifically binds to VEGFR-3 on lymphatic endothelium. We found that the activation of VEGFR-3 attenuated UVB-induced edema formation, associated with a decreased number of CD11b-positive macrophages. Moreover, mutant VEGF-C injection inhibited UVB-induced enlargement of lymphatic vessels and also induced the proliferation of lymphatic endothelial cells. In contrast, treatment with mutant VEGF-C had no effect on blood vessel size or number. These results demonstrate that UVB-induced lymphatic impairment is mediated by downregulation of VEGF-C expression and that the activation of the VEGF-C/VEGFR-3 pathway might represent a feasible target for the prevention of UVB-induced inflammation by promoting lymphangiogenesis. Show more
Journal / seriesJournal of Investigative Dermatology
Pages / Article No.
Organisational unit03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
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