The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells

Biochem Biophys Res Commun. 2005 Nov 11;337(1):241-7. doi: 10.1016/j.bbrc.2005.09.028.


To examine the effects and potential implications for the expression of the two basic fibroblast growth factor (bFGF) receptors, FGFR-1 and FGFR-2, in retinal pigment epithelial (RPE) cells, bFGF-dependent changes in gene expression and RPE cell function were studied. bFGF increased L-type Ca2+ channel activity of RPE cells, which in turn resulted in an increase of vascular endothelial growth factor A (VEGF-A) secretion from RPE cells. Also, both bFGF and direct stimulation of L-type Ca2+ channels by BayK8644 increased the expression of c-fos in RPE cells, to the same extent. bFGF-induced-c-fos expression was reduced by inhibition of FGFR-1, but not by L-type Ca2+ channel inhibition, demonstrating that stimulation of FGFR-1 results in a Ca2+ channel-independent change of gene expression. In contrast, stimulation of FGFR-2 results in a Ca2+ channel-dependent stimulation of VEGF secretion. Furthermore, immunohistological investigation of neovascular tissues obtained from patients with age-related macular degeneration (AMD) revealed FGFR-1 and FGFR-2 expression in the RPE of the diseased tissue. Our findings support the hypothesis that there are two different FGFR-1- and FGFR-2-dependent pathways that modulate the role of bFGF in induction of neovascularisation in AMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium Channels, L-Type / metabolism
  • Cells, Cultured
  • Choroidal Neovascularization / metabolism*
  • Choroidal Neovascularization / physiopathology
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Macular Degeneration / metabolism
  • Macular Degeneration / physiopathology
  • Patch-Clamp Techniques
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / physiopathology
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism


  • Calcium Channels, L-Type
  • Proto-Oncogene Proteins c-fos
  • Receptors, Fibroblast Growth Factor
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • FGFR1 protein, human
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2