Role of fibroblast growth factor-2 isoforms in the effect of estradiol on endothelial cell migration and proliferation

B. Garmy-Susini, E. Delmas, P. Gourdy, M. Zhou, C. Bossard, B. Bugler, F. Bayard, A. Krust, A. C. Prats, T. Doetschman, H. Prats, J. F. Arnal

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Both 17β-estradiol (E2) and fibroblast growth factor-2 (FGF2) stimulate angiogenesis and endothelial cell migration and proliferation. The first goal of this study was to explore the potential link between this hormone and this growth factor. E2-stimulated angiogenesis in SC Matrigel plugs in Fgf2+/+ mice, but not in Fgf2-/- mice. Cell cultures from subcutaneous Matrigel plugs demonstrated that E2 increased both migration and proliferation in endothelial cells from Fgf2+/+ mice, but not from in Fgf2-/- mice. Several isoforms of fibroblast growth factor-2 (FGF2) are expressed: the low molecular weight 18-kDa protein (FGF2lmw) is secreted and activates tyrosine kinase receptors (FGFRs), whereas the high molecular weight (21 and 22 kDa) isoforms (FGF2 hmw) remains intranuclear, but their role is mainly unknown. The second goal of this study was to explore the respective roles of FGF2 isoforms in the effects of E2. We thus generated mice deficient only in the FGF2lmw (Fgf2lmw-/-). E2 stimulated in vivo angiogenesis and in vitro migration in endothelial cells from Fgf2 lmw-/- as it did in Fgf2+/+ mice. E2 increased FGF2hmw protein abundance in endothelial cell cultures from Fgf2 +/+ and Fgf2lmw-/- mice. As shown using siRNA transfection, these effects were FGFR independent but involved FGF2-Interacting Factor, an intracellular FGF2hmw partner. This is the first report for a physiological role for the intracellular FGF2hmw found to mediate the effect of E2 on endothelial cell migration via an intracrine action.

Original languageEnglish (US)
Pages (from-to)1301-1309
Number of pages9
JournalCirculation research
Volume94
Issue number10
DOIs
StatePublished - May 28 2004

Keywords

  • Endothelium
  • Estradiol
  • Growth factor
  • Migration
  • Mouse

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Garmy-Susini, B., Delmas, E., Gourdy, P., Zhou, M., Bossard, C., Bugler, B., Bayard, F., Krust, A., Prats, A. C., Doetschman, T., Prats, H., & Arnal, J. F. (2004). Role of fibroblast growth factor-2 isoforms in the effect of estradiol on endothelial cell migration and proliferation. Circulation research, 94(10), 1301-1309. https://doi.org/10.1161/01.RES.0000127719.13255.81