Ectodomain Shedding of LymphaticVvessel Endothelial Hyaluronan Receptor 1 (LYVE-1) is Induced by Vascular Endothelial Growth Factor A (VEGF-A)
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Date
2016-05-13
Publication Type
Journal Article
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yes
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Abstract
Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a type I transmembrane glycoprotein, is known as one of the most specific lymphatic vessel markers in the skin. In this study, we found that the ectodomain of LYVE-1 undergoes proteolytic cleavage, and this process produces soluble LYVE-1. We further identified the cleavage site for ectodomain shedding and generated an uncleavable mutant of LYVE-1. In lymphatic endothelial cells, ectodomain shedding of LYVE-1 was induced by vascular endothelial growth factor (VEGF)-A, an important factor for angiogenesis and lymphangiogenesis under pathological conditions. VEGF-A-induced LYVE-1 ectodomain shedding was mediated via the extracellular signal-regulated kinase (ERK) and a disintegrin and metalloproteinase (ADAM) 17. Wild-type LYVE-1, but not uncleavable LYVE-1, promoted migration of lymphatic endothelial cells in response to VEGF-A. Immunostaining analyses in human psoriasis skin lesions and VEGF-A transgenic mouse skin suggested that the ectodomain shedding of LYVE-1 occurred in lymphatic vessels undergoing chronic inflammation. These results indicate that the ectodomain shedding of LYVE-1 might be involved in promoting pathological lymphangiogenesis.
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published
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Journal / series
Volume
291 (20)
Pages / Article No.
10490 - 10500
Publisher
American Society for Biochemistry and Molecular Biology
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Subject
ADAM; Endothelial cell; Extracellular signal-regulated kinase (ERK); Hyaluronan; Lymphangiogenesis; Psoriasis; Shedding; Skin; Vascular endothelial growth factor (VEGF); Lymphatic endothelial hyaluronan receptor 1 (LYVE-1)
Organisational unit
03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)