Scholarlink

<p>Lymphatic vessels are essential for tissue homoeostasis and their growth is regulated by vascular endothelial growth factor C (VEGF-C) signalling through VEGFR3. However, how VEGF-C balances lymphatic endothelial cells (LECs) proliferation versus sprouting to ensure functional vessel formation has remained unclear. Using high-fidelity conditional genetics and receptor-specific ligands, we uncover a requirement for the alternative receptor VEGFR2 in VEGF-C-VEGFR3–driven lymphatic vessel sprouting. While activation of VEGFR2 alone fails to induce lymphangiogenesis, VEGFR2 loss abolishes LEC sprouting, but not proliferation, in response to VEGF-C. In contrast, deletion of the VEGFR3 downstream effector PI3Kα completely abrogates lymphangiogenesis. VEGFR2 is activated and found in proximity to VEGFR3 in LECs in vivo, with PI3Kα controlling their relative cell-surface availability and VEGF-C increasing VEGFR2 relative to VEGFR3, thereby priming LECs for sprouting. This receptor coordination balances VEGF-C-driven proliferative and sprouting responses, coupling LEC expansion to vessel growth, ensuring the formation of functional lymphatic networks.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

VEGFR2 is required for VEGF-C–VEGFR3–PI3Kα-mediated sprouting lymphangiogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

查看全文
  • Hans Schoofs,
  • Yan Zhang,
  • Henrik Ortsäter,
  • Mariya Lytvyn,
  • Rui Benedito,
  • Taija Mäkinen

摘要

Lymphatic vessels are essential for tissue homoeostasis and their growth is regulated by vascular endothelial growth factor C (VEGF-C) signalling through VEGFR3. However, how VEGF-C balances lymphatic endothelial cells (LECs) proliferation versus sprouting to ensure functional vessel formation has remained unclear. Using high-fidelity conditional genetics and receptor-specific ligands, we uncover a requirement for the alternative receptor VEGFR2 in VEGF-C-VEGFR3–driven lymphatic vessel sprouting. While activation of VEGFR2 alone fails to induce lymphangiogenesis, VEGFR2 loss abolishes LEC sprouting, but not proliferation, in response to VEGF-C. In contrast, deletion of the VEGFR3 downstream effector PI3Kα completely abrogates lymphangiogenesis. VEGFR2 is activated and found in proximity to VEGFR3 in LECs in vivo, with PI3Kα controlling their relative cell-surface availability and VEGF-C increasing VEGFR2 relative to VEGFR3, thereby priming LECs for sprouting. This receptor coordination balances VEGF-C-driven proliferative and sprouting responses, coupling LEC expansion to vessel growth, ensuring the formation of functional lymphatic networks.