ß-Catenin Signalling Pathway and Its Impact on RPE Cell Cycle: Proliferation vs. Differentiation

Abstract

Purpose: : By using EGF, IGF-1 and VEGF we investigated the role of ß-Catenin signalling pathway in the cell cycle of ARPE19 by induction of cell proliferation and inhibition of differentiation.

Methods: : We measured gene expression of RPE-specific differentiation and proliferation markers as well as transcriptional and translational activity of ß-Catenin signalling markers by FACS and RT-PCR.

Results: : Our data showed a significant decrease of RPE 65, CRALBP and Cytokeratin 18 in ARPE-19 cells stimulated with EGF and IGF-1. In addition, a significant decrease of GSK-3ß and ß-Catenin was observed which was paralleled by an increase of Cyclin D1 expression. Cell cycle studies revealed an increase of ARPE cells in S-G2/M phase after treatment with EGF or IGF-1. VEGF on the other hand lead to a reduction of Cyclin D1 and to an increase of GSK 3ß and ß-Catenin expression which was paralleled by an increase of RPE specific differentiation markers.

Conclusions: : Our data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the ß-Catenin signalling pathway in ARPE-19 cells. Our data suggest that activation of the ß-Catenin signalling pathway may be a key pathway in ARPE-19 cells, which could be activated by different growth factors.

Keywords: retinal pigment epithelium • age-related macular degeneration • aging