The microRNAs miR-302d and miR-93 inhibit TGFB-mediated EMT and VEGFA secretion from ARPE-19 cells.

ABSTRACT

The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies.