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Jong-Jer Lee, I-Hui Yang, Chia-Shiang Chang, Yu-Hsia Kuo, Yi-Hao Chen, Chih-Hsin Chen; CXCL8 regulates the hydrogen peroxide-induced epithelial to mesenchymal transition in retinal pigment epithelial cell line (ARPE-19). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4237.
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© ARVO (1962-2015); The Authors (2016-present)
Epithelial to mesenchymal transition (EMT) is involved in the pathogenesis of proliferative vitreoretinopathy (PVR) and correlated with retinal fibrosis. Oxidative stress is increased following retinal detachment. The aim of this study is to determine the effect of CXCL8 inhibition on regulating the reactive oxygen species-induced expression of EMT biomarkers in retinal pigment epithelial cells.
We evaluated the effect of low concentration hydrogen peroxide (H2O2) on the expression of molecules involved in EMT. Cultured ARPE-19 cells were exposed to low concentration of H2O2 (200 μM) for 4 h. The changes in the expression of CXCL8 and EMT associated genes were determined by real-time PCR (RT-qPCR) and/or western blot analysis. The H2O2-induced cell migration of ARPE-19 was examined by transwell assay.
Treatment of H2O2 induced changes including downregulation of epithelial cadherin and upregulation of a-smooth muscle actin (αSMA), Snail1, Snail2 and phosphorylation of β-catenin after 24 to 48 h in ARPE-19 cells. Cell migration increased by 60.0% (p = 0.003) 24h following the exposure to H2O2. Additionally, the expression of CXCL8 was also increased by 533% (p = 0.001). Reparixin, an inhibitor of CXCL8 receptor, inhibited the H2O2-induced upregulation of αSMA, Snail1, phosphorylation ofβ-catenin, and the cell migration.
Low concentration of H2O2 induces the EMT in ARPE-19 cells. CXCL8 could play an important role in the regulation of EMT induced by oxidative stress in retinal pigment epithelium.
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