Human RPE cells express the FGFR2IIIc and FGFR3IIIc splice variants and FGF9 as a potential high affinity ligand

Exp Eye Res. 2003 Feb;76(2):249-56. doi: 10.1016/s0014-4835(02)00252-x.

Abstract

The expression of splice variants of FGF receptors, which differ in the third Ig domain, was investigated in retinal pigment epithelium (RPE) cells in vitro and in vivo. This region of the protein determines ligand-binding specificity. Additionally, the expression of potential ligands for these receptors was investigated. Expression of FGF receptor transcript alternative splicing was analyzed by RT-PCR/Southern analysis in RPE cells in vitro and in vivo. The expression of FGFs by RT-PCR, in situ hybridization, and immunohistochemistry in sections of the human posterior pole was also investigated. The ARPE-19 cell line expresses only the FGFR2IIIc splice variant and does not express any FGFR3 splice variants in vitro. Two in vivo samples exhibited expression of the FGFR2IIIc and FGFR3IIIc splice variants and no evidence of the corresponding IIIb splice variant. The results from previous studies for these receptors imply that FGF9 or FGF4 could act as ligands. We demonstrated that FGF9 is expressed in a subpopulation of the RPE, as well as photoreceptors and other neurons of the retina. FGF4 was not detected by RT-PCR analysis in RPE cells in vitro. These data suggest that FGF9 may be an autocrine/paracrine factor in the outer retina.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing*
  • Cells, Cultured
  • Female
  • Fibroblast Growth Factor 9
  • Fibroblast Growth Factors / biosynthesis*
  • Fibroblast Growth Factors / genetics
  • Gene Expression
  • Genetic Variation
  • Humans
  • In Situ Hybridization
  • Ligands
  • Male
  • Middle Aged
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / metabolism*
  • Protein-Tyrosine Kinases*
  • RNA, Messenger / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • FGF9 protein, human
  • Fibroblast Growth Factor 9
  • Ligands
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • FGFR2 protein, human
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3