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. 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. Hydrogen peroxide enhances the TGFβ2-mediated epithelial–mesenchymal transition of human retinal pigment epithelial cells, or at least in cell line ARPE-19 cells.

中文翻译：

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过氧化氢增强转化生长因子 beta-2 诱导的 ARPE-19 细胞上皮-间质转化

在视网膜的病理生理学中，上皮-间质转化和氧化应激起着关键作用。为了找出氧化应激与糖尿病性视网膜病变或增殖性视网膜病变之间的关系，我们使用了计算机模拟方法。我们还使用体外研究来检查转化生长因子-β2 (TGFβ2) 和过氧化氢 (H2O2) 对 ARPE-19 细胞上皮-间质转化 (EMT) 的协同作用，分析细胞存活、伤口引起的细胞迁移愈合以及蛋白质和 mRNA 水平上皮-间质转化标志物的表达。将人视网膜色素上皮细胞 (ARPE-19) 在标准条件下培养 24 小时，并加入不同浓度的 TGFβ2、H2O2 及其组合。根据生物信息学研究，信号通路包括缺氧诱导因子（HIF-1）、叉头盒O（FoxO）、磷酸肌醇-3-激酶（PI3K-Akt）和转化生长因子-β（TGFβ-信号传导），生长因子和氧化应激相关蛋白在视网膜病变的发展中发挥重要作用。体外研究表明，H2O2 和 TGFβ2 诱导的氧化应激可增强 ARPE-19 细胞的上皮间质转化。过氧化氢增强人视网膜色素上皮细胞或至少在细胞系 ARPE-19 细胞中 TGFβ2 介导的上皮-间质转化。