title: The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells.
abstract: 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.
authors.affiliation: Augenklinik und Hochschulambulanz, Charité-Universitätsmedizin, Berlin Campus Benjamin Franklin, Berlin, Germany. rita.rosenthal@charite.de
authors.forename: Rita
authors.initials: R
authors.lastname: Rosenthal
authors.forename: Goldis
authors.initials: G
authors.lastname: Malek
authors.forename: Nina
authors.initials: N
authors.lastname: Salomon
authors.forename: Mortiz
authors.initials: M
authors.lastname: Peill-Meininghaus
authors.forename: Linn
authors.initials: L
authors.lastname: Coeppicus
authors.forename: Hendrik
authors.initials: H
authors.lastname: Wohlleben
authors.forename: Soenke
authors.initials: S
authors.lastname: Wimmers
authors.forename: Catherine
authors.initials: C
authors.lastname: Bowes Rickman
authors.forename: Olaf
authors.initials: O
authors.lastname: Strauss
mesh_terms: D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000503:physiopathology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D016760:Proto-Oncogene Proteins c-fos; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2