Nintedanib prevents TGF- ?2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 mu M nintedanib was added to 20 ng/mL trans-forming growth factor beta 2 (TGF-02)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 mu M nintedanib suppressed TGF-02-induced E-cadherin expression decreased and Fibro-nectin, N-cadherin, Vimentin, and a-SMA expression increased. Quantitative real-time PCR results showed that 1 mu M nintedanib decreased TGF-02-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-02-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 mu M nintedanib ameliorated TGF-02-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-02-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.

Automated summary

The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells induced by transforming growth factor beta 2 (TGF-02) is a key mechanism in the fibrosis pathogenesis of proliferative vitreoretinopathy (PVR). However, there are few medications that can inhibit proliferative membranes and cell proliferation in the clinic. In this study, nintedanib, a tyrosine kinase inhibitor, was found to inhibit TGF-02-induced EMT in ARPE-19 cells, suggesting its potential as a pharmacological treatment for PVR.