Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis

Yoshihiro Yamada, Nobuyuki Takakura, Hirofumi Yasue, Hisao Ogawa, Hajime Fujisawa, Toshio Suda

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Neuropilin 1 (NP-1) is a receptor for vascular endothelial growth factor (VEGF) 165 (VEGF165) and acts as a coreceptor that enhances VEGF165 function through tyrosine kinase VEGF receptor 2 (VEGFR-2). Transgenic overexpression of np-1 results in an excess of capillaries and blood vessels and a malformed heart. Thus, NP-1 may have a key role in vascular development. However, how NP-1 regulates vascular development is not well understood. This study demonstrates how NP-1 can regulate vasculogenesis and angiogenesis in vitro and in vivo. In homozygous np-1 mutant (np-1-/-) murine embryos, vascular sprouting was impaired in the central nervous system and pericardium. Para-aortic splanchnopleural mesoderm (P-Sp) explants from np-1-/- mice also had vascular defects in vitro. A monomer of soluble NP-1 (NP-1 tagged with Flag epitope) inhibited vascular development in cultured wild-type P-Sp explants by sequestering VEGF165. In contrast, a dimer of soluble NP-1 (NP-1 fused with the Fc part of human IgG) enhanced vascular development in cultured wild-type P-Sp explants. Moreover, the NP-1-Fc rescued the defective vascular development in cultured np-1-/- P-Sp explants. A low dose of VEGF alone did not promote phosphorylation of VEGFR-2 on endothelial cells from np-1-/- embryos, but simultaneous addition of a low dose of VEGF and NP-1-Fc phosphorylated VEGFR-2 significantly. Moreover, NP-1-Fc rescued the defective vascularity of np-1-/- embryos in vivo. These results suggest that a dimer form of soluble NP-1 delivers VEGF165 to VEGFR-2-positive endothelial cells and promotes angiogenesis.

Original languageEnglish
Pages (from-to)1671-1678
Number of pages8
JournalBlood
Volume97
Issue number6
DOIs
Publication statusPublished - 2001 Mar 15

Fingerprint

Neuropilin-1
Blood Vessels
Mesoderm
Vascular Endothelial Growth Factor Receptor
Embryonic Structures
Endothelial cells
Dimers
Vascular Endothelial Growth Factor A
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-2
Phosphorylation
Pericardium
Blood vessels
Neurology
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Hematology

Cite this

Yamada, Y., Takakura, N., Yasue, H., Ogawa, H., Fujisawa, H., & Suda, T. (2001). Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. Blood, 97(6), 1671-1678. https://doi.org/10.1182/blood.V97.6.1671

Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. / Yamada, Yoshihiro; Takakura, Nobuyuki; Yasue, Hirofumi; Ogawa, Hisao; Fujisawa, Hajime; Suda, Toshio.

In: Blood, Vol. 97, No. 6, 15.03.2001, p. 1671-1678.

Research output: Contribution to journalArticle

Yamada, Y, Takakura, N, Yasue, H, Ogawa, H, Fujisawa, H & Suda, T 2001, 'Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis', Blood, vol. 97, no. 6, pp. 1671-1678. https://doi.org/10.1182/blood.V97.6.1671
Yamada Y, Takakura N, Yasue H, Ogawa H, Fujisawa H, Suda T. Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. Blood. 2001 Mar 15;97(6):1671-1678. https://doi.org/10.1182/blood.V97.6.1671
Yamada, Yoshihiro ; Takakura, Nobuyuki ; Yasue, Hirofumi ; Ogawa, Hisao ; Fujisawa, Hajime ; Suda, Toshio. / Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. In: Blood. 2001 ; Vol. 97, No. 6. pp. 1671-1678.
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