GDF15 Promotes Corneal Neovascularization and Retinoblastoma Cell Progression via AKT/ERK Signal Pathway

Abstract

Objective: We performed this study to investigate the role of growth differentiation factor 15 (GDF15) in corneal neovascularization and retinoblastoma cell progression and the potential mechanisms.Methods: Human retinal endothelial cell (HREC) and retinoblastoma cell line (Y79, RB116 and WERI-Rb1) were treated with recombinant human (rhGDF15, 50 ng/mL) and transfected with small interfering RNA, si-GDF15. Cell migration and proliferation were detected by Scratch assay and CCK8 assay. We performed flow cytometry to measure apoptosis. Tube formation assay for in vitro angiogenesis measurement was used. RT-PCR and western blot were applied to detect the angiogenesis-related factors expression and the level of p-AKT(Ser473), p-AKT(Thr308), AKT, p-ERK1/2(Thr202/Tyr204), and ERK1/2. Tumor growth curve was used after subcutaneous injection of Y79 cells in nude mice and rhsi-GDF15 injection into the tail vein during 21 days.Results: In retinoblastoma cell, rhGDF15 promoted Y79, RB116 and WERI-Rb1 cell migration and suppressed the level of apoptosis. The knock-down of GDF15 significantly inhibited cell migration and promoted apoptosis. In HREC, rhGDF15 increased the tube formation, the level of HIF-1α and SDF, and cell migration, compared with control group, and si-GDF15 played the opposite role. The level of p-AKT(Ser473), p-AKT(Thr308), AKT, p-ERK1/2(Thr202/Tyr204), and ERK1/2 were increased by rhGDF15 in both HREC and retinoblastoma cell lines, contrary to the results of GDF15 knock-down.Conclusion: The downregulation of GDF15 can inhibit corneal angiogenesis and the migration of retinoblastoma cells and promote their apoptosis, which could be dependent on the AKT/ERK pathway.