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Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196865/ https://www.ncbi.nlm.nih.gov/pubmed/25143399 http://dx.doi.org/10.1091/mbc.E14-03-0815 |
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author | Lechuga, Susana Baranwal, Somesh Li, Chao Naydenov, Nayden G. Kuemmerle, John F. Dugina, Vera Chaponnier, Christine Ivanov, Andrei I. |
author_facet | Lechuga, Susana Baranwal, Somesh Li, Chao Naydenov, Nayden G. Kuemmerle, John F. Dugina, Vera Chaponnier, Christine Ivanov, Andrei I. |
author_sort | Lechuga, Susana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4196865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-41968652014-12-30 Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells Lechuga, Susana Baranwal, Somesh Li, Chao Naydenov, Nayden G. Kuemmerle, John F. Dugina, Vera Chaponnier, Christine Ivanov, Andrei I. Mol Biol Cell Articles 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. The American Society for Cell Biology 2014-10-15 /pmc/articles/PMC4196865/ /pubmed/25143399 http://dx.doi.org/10.1091/mbc.E14-03-0815 Text en © 2014 Lechuga, Baranwal, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Lechuga, Susana Baranwal, Somesh Li, Chao Naydenov, Nayden G. Kuemmerle, John F. Dugina, Vera Chaponnier, Christine Ivanov, Andrei I. Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title | Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title_full | Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title_fullStr | Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title_full_unstemmed | Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title_short | Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
title_sort | loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196865/ https://www.ncbi.nlm.nih.gov/pubmed/25143399 http://dx.doi.org/10.1091/mbc.E14-03-0815 |
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