Hydrogen peroxide enhances transforming growth factor beta-2 induced epithelial–mesenchymal transition of ARPE-19 cells

Abstract

Abstract Background In the pathophysiology of the retina, the epithelial–mesenchymal transition and oxidative stress play key roles. To find a relationship between oxidative stress and diabetic retinopathy or proliferative retinopathy, we used an in-silico approach. We also used an in vitro investigation to examine the synergistic effect of transforming growth factors-β2 (TGFβ2) and hydrogen peroxide (H2O2) on the epithelial–mesenchymal transition (EMT) of ARPE-19 cells, analyzing cell survival, cell migration by wound healing, and expression epithelial–mesenchymal transition markers at the protein and mRNA levels. Results For 24 h, human retinal pigment epithelial cells (ARPE-19) were cultured in standard conditions and subjected to various concentrations of TGFβ2, H2O2, and their combinations. According to a bioinformatics study, signaling pathways including hypoxia-inducible factor (HIF-1), forkhead box O (FoxO), phosphoinositide-3-kinase (PI3K-Akt), and transforming growth factors-β (TGFβ-signaling), both growth factors and oxidative stress-associated proteins play a significant role in the development of retinopathies. In vitro studies showed that oxidative stress induced by H2O2 and TGFβ2 enhances the epithelial–mesenchymal transition of ARPE-19 cells. Conclusions Hydrogen peroxide enhances the TGFβ2-mediated epithelial–mesenchymal transition of human retinal pigment epithelial cells, or at least in cell line ARPE-19 cells. Graphical abstract

Keywords

• Epithelial–mesenchymal transition
• Human retinal pigment epithelial cells
• Transforming growth factors-β2
• Hydrogen peroxide
• Oxidative stress
• ARPE-19