Diesel particulate matter2.5 promotes epithelial-mesenchymal transition of human retinal pigment epithelial cells via generation of reactive oxygen species
2020
Lee, Hyesook | Hwang, Bo Hyun | Ji, Seon Yeong | Kim, Min Yeong | Kim, So Young | Park, Cheol | Hong, Su Hyun | Kim, Gi-Young | Song, Kyoung Seob | Hyun, Jin Won | Choi, Yung Hyun
Although several studies have linked PM₂.₅ (particulate matter with a diameter less than 2.5 μm) to ocular surface diseases such as keratitis and conjunctivitis, very few studies have previously addressed its effect on the retina. Therefore, the aim of this study was to evaluate the effect of PM₂.₅ on epithelial-mesenchymal transition (EMT), a process involved in disorders of the retinal pigment epithelial (RPE) on APRE-19 cells. PM₂.₅ changed the phenotype of RPE cells from epithelial to fibroblast-like mesenchymal, and increased cell migration. Exposure to PM₂.₅ markedly increased the expression of mesenchymal markers, but reduced the levels of epithelial markers. Moreover, PM₂.₅ promoted the phosphorylation of MAPKs and the expression of transforming growth factor-β (TGF-β)-mediated nuclear transcriptional factors. However, these PM₂.₅-mediated changes were completely reversed by LY2109761, a small molecule inhibitor of the TGF-β receptor type I/II kinases, and N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger. Interestingly, NAC, but not LY2109761, effectively restored the PM₂.₅-induced mitochondrial defects, including increased ROS, decreased mitochondrial activity, and mitochondrial membrane potential disruption. Collectively, our findings indicate that the TGF-β/Smad/ERK/p38 MAPK signaling pathway is activated downstream of cellular ROS during PM₂.₅-induced EMT. The present study provides the first evidence that EMT of RPE may be one of the mechanisms of PM₂.₅-induced retinal dysfunction.
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