VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment

Masato Murakami, Yujuan Zheng, Masanori Hirashima, Toshio Suda, Yohei Morita, Jun Ooehara, Hideo Ema, Guo Hua Fong, Masabumi Shibuya

研究成果: Article査読

105 被引用数 (Scopus)

抄録

OBJECTIVE - Angiogenesis and lymphangiogenesis are complex phenomena that involve the interplay of several growth factors and receptors. Recently, we have demonstrated that in Keratin-14 (K14) promoter-driven Vegf-A transgenic (Tg) mice, not only angiogenesis but also lymphangiogenesis is stimulated. However, the mechanism by which VEGFR1 is involved in lymphangiogenesis remains unclear. METHODS AND RESULTS - To examine how important the tyrosine kinase (TK) of VEGFR1 is in lymphangiogenesis in K14 Vegf-A Tg mice, we crossed the K14 Vegf-A Tg mice with VEGFR1-TK-deficient mice to generate double mutant K14 Vegf-A Tg Vegfr1 tk mice. K14 Vegf-A Tg Vegfr1 tk mice exhibit a remarkable decrease in lymphangiogensis as well as angiogenesis in subcutaneous tissues. To address the mechanism underlying the decrease in lymphangiogensis, we investigated the recruitment of monocyte-macrophage-lineage cells into the skin. The recruitment of VEGFR1-expressing macrophages driven by VEGF-A was reduced in K14 Vegf-A Tg Vegfr1 tk mice. Vegf-A Tg mice that received VEGFR1-TK-deficient bone marrow showed a reduction of macrophage recruitment, lymphangiogenesis and angiogenesis compared with those in K14 Vegf-A Tg mice. CONCLUSIONS - VEGFR1 signaling promotes lymphangiogenesis as well as angiogenesis mainly by increasing bone marrow-derived macrophage recruitment.

本文言語English
ページ(範囲)658-664
ページ数7
ジャーナルArteriosclerosis, Thrombosis, and Vascular Biology
28
4
DOI
出版ステータスPublished - 2008 4

ASJC Scopus subject areas

  • 循環器および心血管医学

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