Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires αvβ3

Abha Sahni, Charles W. Francis

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

We have shown previously that fibrin(ogen) binding potentiates the capacity of fibroblast growth factor 2 (FGF-2) to stimulate endothelial cell (EC) proliferation. We have now investigated the receptor requirement for EC proliferation by fibrinogen-bound FGF-2. ECs were cultured with 25 ng/mL FGF-2 with or without 10 μg/mL fibrinogen, and proliferation was measured as 3H-thymidine incorporation. Proliferation was increased 2.4 ± 0.5-fold over medium alone with FGF-2 and increased significantly more to 4.0 ± 0.7-fold with fibrinogen and FGF-2 (P < .005). Addition of 7E3 or LM609, antibodies to αvβ3, inhibited EC proliferation with fibrinogen-bound FGF-2 by 80% ± 8% (P < .001) or 67% ± 14% (P < .002), respectively, to levels significantly less than that observed with FGF-2 alone (P < .001). Neither LM609 nor 7E3 exhibited any inhibition of activity with FGF-2 alone. Peptide GRGDS caused dose-dependent inhibition of proliferation by fibrinogen-bound FGF-2 of 31% ± 8%, 45% ± 9%, and 68% ± 11% at 0.25, 0.5, and 1 mM, respectively. Coimmunoprecipitation and immunofluorescence studies demonstrated a direct specific association between αvβ3 and FGF receptor 1 (FGFR1) in ECs and fibroblasts when exposed to both FGF-2 and fibrinogen but not with vitronectin. We conclude that fibrinogen binding of FGF-2 enhances EC proliferation through the coordinated effects of colocalized αvβ3 and FGFR1.

Original languageEnglish (US)
Pages (from-to)3635-3641
Number of pages7
JournalBlood
Volume104
Issue number12
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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