Matrix Rigidity Mediates TGFβ1-induced Epithelial-Myofibroblast Transition by Controlling Cytoskeletal Organization and MRTF-A Localization

摘要: Myofibroblasts mediate normal wound healing and upon chronic activation can contribute to the development of pathological conditions including organ fibrosis cancer. develop from epithelial cells through an epithelial-mesenchymal transition (EMT) during which exhibit drastic morphological changes upregulate cytoskeletal associated proteins that enable exertion large contractile forces remodeling surrounding microenvironment. Increased matrix rigidity is a hallmark tumor progression mechanical tension has been identified as regulator EMT; however, mechanisms governing regulation EMT are not completely understood. Here, we find regulates transforming growth factor (TGF)-β1-induced EMT, with rigid substrata enabling increased myofibroblast marker expression, cell morphology changes, reorganization while soft matrices block these changes. Furthermore, controls subcellular localization myocardin related transcription (MRTF)-A, protein expression contributes acquisition myogenic features EMT. Results studies provide insight into how biophysical cues may suggest ways enhance or engineer therapeutic solutions for J. Cell. Physiol. 230: 1829–1839, 2015. © 2014 Wiley Periodicals, Inc.