title: Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A.
abstract: During epithelial-mesenchymal transition (EMT) epithelial cells lose cell-cell adhesion, exhibit morphological changes, and upregulate the expression of cytoskeletal proteins. Previous studies have demonstrated that complete disruption of cell-cell contact can promote transforming growth factor (TGF)-β1-induced EMT and the expression of the myofibroblast marker alpha smooth muscle actin (αSMA). Furthermore, increased cell spreading mediates TGFβ1-induced αSMA expression during EMT. Here, we sought to examine how the presence of partial cell-cell contacts impacts EMT. A microfabrication approach was employed to decouple the effects of cell-cell contact and cell-matrix adhesion in TGFβ1-induced EMT. When cell spreading is controlled, the presence of partial cell-cell contacts enhances expression of αSMA. Moreover, cell spreading and intercellular contacts together control the subcellular localization of activated Notch1 and myocardin related transcription factor (MRTF)-A. Knockdown of Notch1 or MRTF-A as well as pharmacological inhibition of these pathways abates the cell-cell contact mediated expression of αSMA. These data suggest that the interplay between cell-matrix adhesion and intercellular adhesion is an important determinant for some aspects of TGFβ1-induced EMT.
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: O'Connor
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Krunal
authors.initials: K
authors.lastname: Mistry
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Dayne
authors.initials: D
authors.lastname: Detweiler
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Clayton
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA.|Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Gomez
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051379:Mice; D058628:Myofibroblasts / Q000502:physiology*; D051881:Receptor, Notch1 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000199:Actins; C511173:Mrtfa protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse