title: β-Catenin/CBP-Dependent Signaling Regulates TGF-β-Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology and Molecular Medicine, McMaster Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Aftab
authors: A
authors: Taiyab
authors: Department of Pathology and Molecular Medicine, McMaster Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Anna
authors: A
authors: Korol
authors: Department of Pathology and Molecular Medicine, McMaster Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Paula A
authors: PA
authors: Deschamps
authors: Department of Pathology and Molecular Medicine, McMaster Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Judith A
authors: JA
authors: West-Mays
mesh_terms: D000199:Actins; D000818:Animals; D015153:Blotting, Western; D058442:Capsule Opacification / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D015398:Signal Transduction; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology*; D051176:beta Catenin / Q000494:pharmacology*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D053781:Transforming Growth Factor beta2; D051176:beta Catenin; C020324:fascin