While TGF-beta 1 is known to induce epithelial mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-beta 1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-beta 1 inhibited GSK-beta 3 by accelerating phosphorylation at ser9. GSK-3 beta inhibitor or knockdown of GSK-beta 3 resulted in enhanced TGF-beta 1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-beta 3 overexpression and PI3K/AKT inhibitor. Importantly, GSK-beta 3 also mediated metabolic reprogramming in TGF-beta 1-treated cells. Our results indicate that GSK-3 beta plays a pivotal role in TGF-beta 1-mediated EMT in ARPE-19 cells. (C) 2017 Elsevier Inc. All rights reserved.