Activation of the β-Catenin Signaling Pathway and Its Impact on RPE Cell Cycle

Abstract

The data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the beta-catenin signaling pathway in ARPE-19 cells. The data suggest that activation of the beta-catenin signaling pathway may be key in activating ARPE-19 cells by different growth factors.

Epidermal growth factor: the driving force in initiation of RPE cell proliferation

“…In addition, we evaluated cell-cycle studies to prove whether epidermal growth factor (EGF) is a possible candidate for promoting cell proliferation and restriction of differentiation via activation of the beta-catenin signaling pathway, part of the canonic Wnt pathway, as EGF is known to induce proliferation in other epithelial cell types [14, 15]. Our data identified EGF as a potent initiator of RPE proliferation via activation of the ß-catenin signaling pathway after 48 h of treatment, showing a significant decrease of RPE 65, CRALBP and cytokeratin 18 in ARPE-19 cells [13]. In addition an increase of cyclin D1 expression and a significant decrease of GSK-3ß and ß-catenin were observed.…”

“…Therefore young or rejuvenated cells would be the best candidates for successful RPE transplantation so that AMD patients might recover vision again [11, 12]. In our first study, we examined that the first step of such a rejuvenation process is the “push back” of cells into G1 phase of the cell cycle to provide an insight into an active cell cycle for those cells indicating induced proliferation of cells and reduced differentiation [13]. Therefore, we chose different RPE-specific differentiation markers (retinal pigment epithelium-specific Protein 65 (RPE 65), cellular retinaldehyde-binding protein (CRALBP), cytokeratin 18), proliferation markers (cyclin D1) and Wnt markers (beta-catenin (ß-catenin), glycogen synthase kinase-3beta (GSK-3ß)) to investigate proliferation vs. differentiation in ARPE-19 cells on the translational level via fluorescence activated cell sorting (FACS) and on the transcriptional level via reverse transcription – polymerase chain reaction (RT-PCR).…”

“…In addition an increase of cyclin D1 expression and a significant decrease of GSK-3ß and ß-catenin were observed. Cell-cycle studies revealed an increase of ARPE cells in S-G2/M phase after 48 h of EGF treatment [13]. …”

“…Short incubation times enhance RPE cell quality for feasible rejuvenation and subsequent autologous transplantation of RPE cells [18]. As EGF turned out to be that powerful after 48 h incubation [13], we investigated its mitogenic effect on the induction of RPE cell proliferation after shorter incubation times (24 h).…”

Retinal Toxicity of Intravitreal Trastuzumab in a Rabbit Model: Preliminary Results of an Experimental Study

“…1 There is evidence indicating that EGFR signaling is involved in a variety of cellular processes, such as growth, differentiation, and survival of retinal pigment epithelial (RPE) cells in vitro. [2][3][4][5] Interestingly enough, Sugino et al supported that the EGF and its signaling pathways are significant factors associated with the survival, proliferation, adhesion, and migration of RPE in age-related macular degeneration models. 6 In addition, the EGF is known to be an angiogenic factor, as well as an upregulator of the expression of other angiogenic factors, such as the vascular endothelial growth factor (VEGF) and interleukin-8.…”