Cell-cell contact and matrix adhesion promote ?SMA expression during TGF?1-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)-?1-induced EMT and the expression of the myofibroblast marker alpha smooth muscle actin (?SMA). Furthermore, increased cell spreading mediates TGF?1-induced ?SMA 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 TGF?1-induced EMT. When cell spreading is controlled, the presence of partial cell-cell contacts enhances expression of ?SMA. 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 ?SMA. These data suggest that the interplay between cell-matrix adhesion and intercellular adhesion is an important determinant for some aspects of TGF?1-induced EMT.

SUBMITTER: O'Connor JW 

PROVIDER: S-EPMC4872162 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature