LYTAK1, a TAK1 inhibitor, suppresses proliferation and epithelial-mesenchymal transition in retinal pigment epithelium cells

Abstract

The proliferation of retinal pigment epithelium (RPE) cells following epithelial-mesenchymal transition (EMT) is critical in proliferative vitreoretinopathy (PVR), which results in retinal detachment and the loss of vision. The current study was conducted to examine the importance of transforming growth factor β-1 (TGF-β1)-activated kinase 1 (TAK1) inhibitor (LYTAK1) in regulating EMT and the proliferation of RPE cells. RPE cells were pre-treated with increasing concentrations of LYTAK1 prior to treatment with TGF-β1 for 24 h. The effect of LYTAK1 on RPE cell proliferation was examined using a Cell Counting kit-8 assay. The expression levels of TAK1, smooth muscle actin, fibronectin, p-Smad2, p-Smad3, nuclear factor (NF)-κB p65 and IκB kinase α were detected by western blotting. LYTAK1 suppressed the proliferation and migration of RPE cells. Additionally, LYTAK1 significantly prevented TGF-β1-induced EMT by decreasing the levels of fibronectin and α-smooth muscle actin. It was demonstrated that the effects of LYTAK1 were via the Smad signaling pathway. The present study also determined, that the underlying mechanism of the effects of LYTAK1 on EMT in RPE cells involves downregulation of the NF-κB signaling pathway. In conclusion, TAK1 transcription factor was shown to be important in TGF-β1-induced EMT in human RPE cells. Thus, the results of this study aid in elucidating the pathogenesis of human PVR. In addition, this study suggests that specific inhibition by LYTAK1 may provide a novel approach for the treatment and prevention of PVR.