?-Catenin/CBP-Dependent Signaling Regulates TGF-?-Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells.

ABSTRACT: Transforming growth factor-?-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-?-induced PCO have not been fully characterized. Here, we focus on examining the role of ?-catenin/cyclic AMP response element-binding protein (CREB)-binding protein (CBP) and ?-catenin/T-cell factor (TCF)-dependent signaling in regulating cytoskeletal dynamics during TGF-?-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-?2 in the presence or absence of the ?-catenin/CBP interaction inhibitor, ICG-001, or the ?-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-?, and colocalized with F-actin filaments. Inhibition of ?-catenin/CBP interactions, but not ?-catenin/TCF interactions, led to a decrease in TGF-?-induced fascin and stress fiber formation, as well as a decrease in the expression of known markers of EMT, ?-smooth muscle actin (?-SMA) and matrix metalloproteinase 9 (MMP9). In addition, inhibition of ?-catenin/CBP-dependent signaling also prevented TGF-?-induced downregulation of epithelial cadherin (E-cadherin) in lens explants.We show that ?-catenin/CBP-dependent signaling regulates fascin, MMP9, and ?-SMA expression during TGF-?-induced EMT. We demonstrate that ?-catenin/CBP-dependent signaling is crucial for TGF-?-induced EMT in the lens.

SUBMITTER: Taiyab A 

PROVIDER: S-EPMC5089212 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature