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γ‐Cytoplasmic Actin Modulates Epithelial to Myofibroblast Transition in Lung Epithelial Cells
Author(s) -
Baranwal Somesh,
Gupta Pooja,
Ivanov Andrei I
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.132.7
Subject(s) - myofibroblast , microbiology and biotechnology , actin , cytoskeleton , cytoplasm , a549 cell , actin cytoskeleton , biology , focal adhesion , fibrosis , chemistry , cell , signal transduction , pathology , medicine , biochemistry
Epithelial to myofibroblast transition (EMyT) plays an important role in tumor progression and tissue fibrosis. EMyT is accompanied by dramatic changes in the organization of the actin cytoskeleton, although the roles of different cytoskeletal proteins in modulating such transition remain poorly understood. In the present study, we observed that siRNA‐mediated knock‐down of γ‐ cytoplasmic actin (γ‐CYA) but not β‐cytoplasmic actin induced EMyT in A549 lung epithelial cells. The EMyT was manifested by increased expression of α‐smooth muscle actin, L‐caldesmon and other contractile proteins along with disruption of focal adhesions and inhibition of cell migration. Induction of EMyT in γ‐CYA‐depleted cells depended on activation of a transcriptional regulator, Serum Response Factor and nuclear translocation of its coactivators, MRTF‐A and MRTF‐B. Furthermore, immunoprecipitation analysis revealed selective interactions of MRTFs with γ‐CYA. Finally, pharmacological inhibition of Rho kinase attenuated induction of EMyT in γ‐CYA‐depleted cells. Together, this study identifies γ‐CYA as a potent suppressor of EMyT in epithelial cells that may play roles in regulating tumor progression and tissue fibrosis. Supported by NIH grant DK083968 and DK084953 to Andrei I Ivanov