Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells.
Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells.
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DOI：
10.1091/mbc.e14-03-0815
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发表时间：
2014-10-15
影响因子：
3.3
通讯作者：
Ivanov AI
中科院分区：
文献类型：
--
作者：
Lechuga S;Baranwal S;Li C;Naydenov NG;Kuemmerle JF;Dugina V;Chaponnier C;Ivanov AI
Loss of γ-cytoplasmic actin induces epithelial-to-myofibroblast transition (EmyT), which depends on activation of SRF and its cofactor, MRTF, formin-mediated actin polymerization, and activated Rho GTPase. This demonstrates a unique role of γ-cytoplasmic actin in regulating the epithelial phenotype and the suppression of EmyT. Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood. In the present study, we observed that selective siRNA-mediated knockdown of γ-cytoplasmic actin (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition (EMyT) of different epithelial cells. The EMyT manifested by increased expression of α-smooth muscle actin and other contractile proteins, along with inhibition of genes responsible for cell proliferation. Induction of EMyT in γ-CYA–depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B. Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction. Our findings demonstrate a previously unanticipated, unique role of γ-CYA in regulating epithelial phenotype and suppression of EMyT that may be essential for cell differentiation and tissue fibrosis.
