Upregulation of neuropilin-1 by basic fibroblast growth factor enhances vascular smooth muscle cell migration in response to VEGF

Wenbiao Liu, Alexander A. Parikh, Oliver Stoeltzing, Fan Fan, Marya F. McCarty, Jane Wey, Daniel J. Hicklin, Lee M. Ellis

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Neuropilin-1 (NRP-1) is a co-receptor for vascular endothelial growth factor (VEGF). During neovascularization, vascular smooth muscle cells (VSMCs) and pericytes modulate the function of endothelial cells. Factors that mediate NRP-1 in human VSMCs (hVSMCs) remain to be elucidated. We studied various angiogenic cytokines to identify factors that increase NRP-1 expression in hVSMCs. Treatment of hVSMCs with basic fibroblast growth factor (b-FGF) induced expressions of NRP-1 mRNA and protein whereas epidermal growth factor, insulin-like growth factor-1, and interleukin-1β did not. b-FGF induced phosphorylation of Erk-1/2 and JNK. MEK1/2 and nuclear factor kappa B (NF-κB) inhibitors (U0126 and TLCK, respectively) blocked the ability of b-FGF to induce NRP-1 mRNA expression, but inhibition of JNK (SP600125) or PI3-kinase activity (wortmannin) did not. Further, the increase in NRP-1 expression by b-FGF enhanced hVSMCs migration in response to VEGF165. This effect was dependent on the binding of VEGF165 to VEGFR-2, as blocking antibodies to VEGFR-2, but not VEGFR-1, inhibited VEGF 165-induced migration. In conclusion, b-FGF increased NRP-1 expression in hVSMCs that in turn enhance the effect of VEGF165 on cell migration. The enhanced migration of hVSMCs was mediated through binding of VEGF165 to both NRP-1 and VEGFR-2, as inhibition of VEGFR-2 on these cells blocked the effect of VEGF-mediated cell migration.

Original languageEnglish (US)
Pages (from-to)206-212
Number of pages7
JournalCytokine
Volume32
Issue number5
DOIs
StatePublished - Dec 7 2005
Externally publishedYes

Keywords

  • Angiogenesis
  • Neuropilin-1
  • Pericytes
  • VEGF
  • b-FGF

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Biochemistry
  • Immunology and Allergy
  • Immunology

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