Abstract
Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. The effect of oxidative stress alone or together with transforming growth factor-beta 2 (TGF-β2) on epithelial-mesenchymal transformation (EMT) is not fully understood in RPE. TGF-β2 induced the upregulation EMT markers including α-smooth muscle actin (α-SMA), Snail, and Slug and downregulation of E-cadherin (E-cad) in ARPE-19 cells. Hydrogen peroxide (H2O2) not only upregulated α-SMA but also enhanced the effect of TGF-β2 on the expression of Snail and Slug. The CXCL family of cytokines could be the mediators of EMT induced by H2O2 and TGF-β2. H2O2 induced CXCL1, that upregulated α-SMA and fibronectin. Both SB225002, an inhibitor of CXCR2, and antioxidant N-acetylcysteine suppressed the TGF-β2-induced EMT in ARPE-19 cells. Taken together, the results suggest that oxidative stress enhanced TGF-β2-induced EMT through the possible autocrine effect of CXCL1 on CXCR2 in ARPE-19 cells.
Highlights
Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness
To assess the effect of oxidative stress and TGF-β on epithelial-mesenchymal transformation (EMT), ARPE-19 cell line was treated with H2O2 (100–400 μM) and/or recombinant human TGF-β2 for analyzing the expression of EMT markers including E-cad, α-smooth muscle actin (α-SMA), and fibronectin (FN)
We demonstrated that low level of oxidative stress could potentially facilitate TGF-β2-induced EMT in ARPE-19 cells
Summary
Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. In a study involving lung fibrosis, Jain et al showed that inhibition of transforming growth factor-beta (TGF-β)-induced reactive oxygen species (ROS) generation decreased the expression of pro-fibrotic genes, including α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Increase in ROS levels has been demonstrated to be associated with the regulation of expression of CXC chemokines in epithelial tumor cells[15]. The effect of ROS in the regulation of expression of CXC chemokines and their role in EMT of RPE cells www.nature.com/scientificreports is still not fully understood. The purpose of this study was to evaluate the effect of ROS in TGF-β2-induced EMT and the involvement of CXC chemokines in the regulation of EMT-associated genes in RPE cells
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