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Aftab Taiyab, Anna Korol, Paula A. Deschamps, Judith A. West-Mays; β-Catenin/CBP–Dependent Signaling Regulates TGF-β–Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(13):5736-5747. doi: https://doi.org/10.1167/iovs.16-20162.
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© ARVO (1962-2015); The Authors (2016-present)
Transforming growth factor-β–induced epithelial–mesenchymal transition (EMT) is one of the main causes of posterior capsular opacification (PCO) or secondary cataract; however, the signaling events involved in TGF-β–induced PCO have not been fully characterized. Here, we focus on examining the role of β-catenin/cyclic AMP response element–binding protein (CREB)-binding protein (CBP) and β-catenin/T-cell factor (TCF)-dependent signaling in regulating cytoskeletal dynamics during TGF-β–induced EMT in lens epithelial explants.
Rat lens epithelial explants were cultured in medium M199 in the absence of serum. Explants were treated with TGF-β2 in the presence or absence of the β-catenin/CBP interaction inhibitor, ICG-001, or the β-catenin/TCF interaction inhibitor, PNU-74654. Western blot and immunofluorescence experiments were carried out and analyzed.
An increase in the expression of fascin, an actin-bundling protein, was observed in the lens explants upon stimulation with TGF-β, and colocalized with F-actin filaments. Inhibition of β-catenin/CBP interactions, but not β-catenin/TCF interactions, led to a decrease in TGF-β–induced fascin and stress fiber formation, as well as a decrease in the expression of known markers of EMT, α-smooth muscle actin (α-SMA) and matrix metalloproteinase 9 (MMP9). In addition, inhibition of β-catenin/CBP–dependent signaling also prevented TGF-β–induced downregulation of epithelial cadherin (E-cadherin) in lens explants.
We show that β-catenin/CBP–dependent signaling regulates fascin, MMP9, and α-SMA expression during TGF-β–induced EMT. We demonstrate that β-catenin/CBP–dependent signaling is crucial for TGF-β–induced EMT in the lens.
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