PURPOSE: The aim of this study was to investigate the expression changes of epithelial mesenchymal transition (EMT)-related molecules induced by TGF-β signaling in a human corneal epithelial cell line (HCECs). METHODS: The cellular response to TGF-β was evaluated by immunoblotting, quantitative real-time RT-PCR, and immunofluorescence microscopy in HCECs. RESULTS: TGF-β significantly increased mRNA expression of SNAI1, SNAI2, VIM, and FN1, but not TWIST1 through Smad and non-Smad pathways in HCECs. Protein expression of a mesenchymal marker N-cadherin was dose-dependently increased and that of an epithelial marker of E-cadherin was decreased by TGF-β. TGF-β, but not EGF, mediated the EMT-like morphologic changes. Both TGF-β and EGF were capable of upregulating SNAI1 and SNAI2 by about two-fold within a short response time. However, a detailed time course analysis revealed drastically different expression patterns, with TGF-β mediating a sustained upregulation of SNAI1 and SNAI2 for at least for 6 days and EGF allowing a return to the baseline expression values after 8 ∼ 12 h. These data indicate that TGF-β, but not EGF, induces sustained upregulation of SNAI1 and SNAI2 in HCECs. CONCLUSIONS: TGF-β induces sustained upregulation of SNAI1 and SNAI2 through Smad and non-Smad pathways, EMT-like morphologic changes, downregulation of E-cadherin, and upregulation of N-cadherin in HCECs. The authors' findings provide insight into the TGF-β signaling and the temporal expression patterns of EMT-inducible transcription factors in HCECs.
PURPOSE: The aim of this study was to investigate the expression changes of epithelial mesenchymal transition (EMT)-related molecules induced by TGF-β signaling in a human corneal epithelial cell line (HCECs). METHODS: The cellular response to TGF-β was evaluated by immunoblotting, quantitative real-time RT-PCR, and immunofluorescence microscopy in HCECs. RESULTS: TGF-β significantly increased mRNA expression of SNAI1, SNAI2, VIM, and FN1, but not TWIST1 through Smad and non-Smad pathways in HCECs. Protein expression of a mesenchymal marker N-cadherin was dose-dependently increased and that of an epithelial marker of E-cadherin was decreased by TGF-β. TGF-β, but not EGF, mediated the EMT-like morphologic changes. Both TGF-β and EGF were capable of upregulating SNAI1 and SNAI2 by about two-fold within a short response time. However, a detailed time course analysis revealed drastically different expression patterns, with TGF-β mediating a sustained upregulation of SNAI1 and SNAI2 for at least for 6 days and EGF allowing a return to the baseline expression values after 8 ∼ 12 h. These data indicate that TGF-β, but not EGF, induces sustained upregulation of SNAI1 and SNAI2 in HCECs. CONCLUSIONS: TGF-β induces sustained upregulation of SNAI1 and SNAI2 through Smad and non-Smad pathways, EMT-like morphologic changes, downregulation of E-cadherin, and upregulation of N-cadherin in HCECs. The authors' findings provide insight into the TGF-β signaling and the temporal expression patterns of EMT-inducible transcription factors in HCECs.
Authors: V C Padmakumar; Kelsey Speer; Sonali Pal-Ghosh; Katelyn E Masiuk; Andrew Ryscavage; Samuel L Dengler; Shelly Hwang; John C Edwards; Vincenzo Coppola; Lino Tessarollo; Mary Ann Stepp; Stuart H Yuspa Journal: Am J Pathol Date: 2012-05-18 Impact factor: 4.307
Authors: Yixuan Li; Xiangyang Zhang; Shaoqi Zhu; Eden A Dejene; Weiqun Peng; Antonia Sepulveda; Edward Seto Journal: Cancer Res Date: 2020-06-15 Impact factor: 12.701
Authors: Jong-Ho Cha; Hee-Jun Wee; Ji Hae Seo; Bum Ju Ahn; Ji-Hyeon Park; Jun-Mo Yang; Sae-Won Lee; Ok-Hee Lee; Hyo-Jong Lee; Irwin H Gelman; Ken Arai; Eng H Lo; Kyu-Won Kim Journal: Nat Commun Date: 2014-09-17 Impact factor: 14.919