Journal article

Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A).

  • Nishida-Fukuda H From the Departments of Dermatology, Biochemistry and Molecular Genetics, and.
  • Araki R From the Departments of Dermatology.
  • Shudou M Bioscience, Advanced Research Support Center (ADRES), Ehime University Graduate School of Medicine, Toon 791-0295, Japan.
  • Okazaki H From the Departments of Dermatology.
  • Tomono Y Division of Molecular and Cell Biology, Shigei Medical Research Institute, Okayama 701-0202, Japan.
  • Nakayama H Biochemistry and Molecular Genetics, and Strategic Young Researcher Overseas Visiting Program for Accelerating Brain Circulation, Japan Society for the Promotion of Science (JSPS), 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan, Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon 791-0295, Japan.
  • Fukuda S Biochemistry and Molecular Genetics, and Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon 791-0295, Japan.
  • Sakaue T Biochemistry and Molecular Genetics, and Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon 791-0295, Japan.
  • Shirakata Y From the Departments of Dermatology.
  • Sayama K From the Departments of Dermatology.
  • Hashimoto K From the Departments of Dermatology.
  • Detmar M Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich CH-8093, Switzerland, and.
  • Higashiyama S Biochemistry and Molecular Genetics, and Strategic Young Researcher Overseas Visiting Program for Accelerating Brain Circulation, Japan Society for the Promotion of Science (JSPS), 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan, Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon 791-0295, Japan.
  • Hirakawa S From the Departments of Dermatology, Strategic Young Researcher Overseas Visiting Program for Accelerating Brain Circulation, Japan Society for the Promotion of Science (JSPS), 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan, Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan hirakawa@hama-med.ac.jp.
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  • 2016-03-12
Published in:
  • The Journal of biological chemistry. - 2016
English 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/168037
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