GSK3β attenuates TGF-β1 induced epithelial–mesenchymal transition and metabolic alterations in ARPE-19 cells
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)
While TGF-β1 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-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor. Importantly, GSK-3β also mediated metabolic reprogramming in TGF-β1-treated cells. Our results indicate that GSK-3β plays a pivotal role in TGF-β1-mediated EMT in ARPE-19 cells. - Highlights: • GSK-3β mediates epithelial-mesenchymal transition in TGF-β1 treated ARPE-19 cells. • GSK-3β regulates cell migration and collagen contraction of ARPE-19 cells. • TGF-β1 induces extracellular metabolomic changes of ARPE-19 cells via a GSK-3β-dependent mechanism.
- OSTI ID:
- 22697003
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 486; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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