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Biochem Biophys Res Commun. 2005 Nov 11;337(1):241-7.

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

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1
Augenklinik und Hochschulambulanz, Charité-Universitätsmedizin, Berlin Campus Benjamin Franklin, Berlin, Germany. rita.rosenthal@charite.de

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.

PMID:
16188231
DOI:
10.1016/j.bbrc.2005.09.028
[Indexed for MEDLINE]
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