期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 42, 期 1, 页码 123-130出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2018.3612
关键词
VAS2870; NADPH oxidase 4; proliferation; epithelial-to-mesenchymal transition; retinal pigment epithelial cells; proliferative vitreoretinopathy; alpha-smooth muscle actin; cyclin D1; E-cadherin
资金
- Shannxi Provincial Natural Science Foundation of China [2014JM2-8190]
NADPH oxidases (NOXs) are important in the pathophysiology of fibrotic diseases. The expression and activity of NOXs are regulated by growth factors, including transforming growth factor (TGF-beta). The proliferation of retinal pigment epithelial (RPE) cells following epithelial-to-mesenchymal transition (EMT) is a major pathological change involved in proliferative vitreoretinopathy (PVR). The aim of the present study was to determine the effects of the novel NOX inhibitor VAS2870 on the TGF-beta-dependent expression of NOX4 and associated cellular events in RPE cells. Cell viability was examined using a Cell Counting Kit-8 assay and cell cycle progression was detected by flow cytometric analysis. Immunofluorescence analysis and western blot analysis were performed to assess EMT. It was found that TGF-beta increased the expression of NOX4 and that pre-incubation with VAS2870 eliminated this effect. Additionally, TGF-beta promoted RPE migration and increased EMT. Pre-incubation with VAS2870 significantly prevented TGF-beta 2-induced EMT by decreasing the levels of a-smooth muscle actin and E-cadherin, and also inhibited the migratory ability of the RPE cells, as demonstrated by scratch assays. Finally, VAS2870 suppressed the proliferation of RPE cells, and led to G(1)-phase cell cycle arrest and a significant downregulation of the expression of cyclin D1. In conclusion, the pharmacological inhibition of NOX may be a promising tool for the treatment of PVR.
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