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A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation
BACKGROUND: Pulmonary fibrosis initiates a pneumonic cascade that leads to fibroblast dysfunction characterized by excess proliferation. Anoikis is a physiological process that ensures tissue development and homeostasis. Researchers have not clearly determined whether disruption of anoikis is involv...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881884/ https://www.ncbi.nlm.nih.gov/pubmed/35216634 http://dx.doi.org/10.1186/s13578-022-00761-2 |
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author | Yin, Juan Wang, Jing Zhang, Xinxin Liao, Yan Luo, Wei Wang, Sha Ding, Jiawei Huang, Jie Chen, Mengling Wang, Wei Fang, Shencun Chao, Jie |
author_facet | Yin, Juan Wang, Jing Zhang, Xinxin Liao, Yan Luo, Wei Wang, Sha Ding, Jiawei Huang, Jie Chen, Mengling Wang, Wei Fang, Shencun Chao, Jie |
author_sort | Yin, Juan |
collection | PubMed |
description | BACKGROUND: Pulmonary fibrosis initiates a pneumonic cascade that leads to fibroblast dysfunction characterized by excess proliferation. Anoikis is a physiological process that ensures tissue development and homeostasis. Researchers have not clearly determined whether disruption of anoikis is involved in pulmonary fibrosis. RESULTS: Here, we investigated the mechanism by which silica induces fibroblast activation via anoikis resistance and subsequent fibrosis. Anoikis of lung fibroblasts, alveolar epithelial cells and endothelial cells during the process of fibrosis was detected using CCK-8, western blot, cell count and flow cytometry (FCM) assays. Although the three cell types showed similar increases in proliferation, the expression of NTRK2, a marker of anoikis resistance, was upregulated specifically in fibroblasts, indicating the unique proliferation mechanism of fibroblasts in pulmonary fibrosis, which may be related to anoikis resistance. Furthermore, the CRISPR/Cas9 system was used to investigate the molecular mechanism of anoikis resistance; the SiO(2)-induced inflammatory response activated the MAPK/PI3K signaling pathway in lung fibroblasts and then induced the expression of the ZC3H4 protein, which specifically mediated anoikis resistance, followed by pulmonary fibrosis. CONCLUSIONS: The current study revealed a specific pattern of fibroblast proliferation, and strategies targeting anoikis resistance may inhibit the pathological process of pulmonary fibrosis. This result provides a new approach for treating pulmonary fibrosis and new insights into the potential application of ZC3H4 in the development of novel therapeutic strategies for mitigating pulmonary fibrosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00761-2. |
format | Online Article Text |
id | pubmed-8881884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88818842022-02-28 A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation Yin, Juan Wang, Jing Zhang, Xinxin Liao, Yan Luo, Wei Wang, Sha Ding, Jiawei Huang, Jie Chen, Mengling Wang, Wei Fang, Shencun Chao, Jie Cell Biosci Research BACKGROUND: Pulmonary fibrosis initiates a pneumonic cascade that leads to fibroblast dysfunction characterized by excess proliferation. Anoikis is a physiological process that ensures tissue development and homeostasis. Researchers have not clearly determined whether disruption of anoikis is involved in pulmonary fibrosis. RESULTS: Here, we investigated the mechanism by which silica induces fibroblast activation via anoikis resistance and subsequent fibrosis. Anoikis of lung fibroblasts, alveolar epithelial cells and endothelial cells during the process of fibrosis was detected using CCK-8, western blot, cell count and flow cytometry (FCM) assays. Although the three cell types showed similar increases in proliferation, the expression of NTRK2, a marker of anoikis resistance, was upregulated specifically in fibroblasts, indicating the unique proliferation mechanism of fibroblasts in pulmonary fibrosis, which may be related to anoikis resistance. Furthermore, the CRISPR/Cas9 system was used to investigate the molecular mechanism of anoikis resistance; the SiO(2)-induced inflammatory response activated the MAPK/PI3K signaling pathway in lung fibroblasts and then induced the expression of the ZC3H4 protein, which specifically mediated anoikis resistance, followed by pulmonary fibrosis. CONCLUSIONS: The current study revealed a specific pattern of fibroblast proliferation, and strategies targeting anoikis resistance may inhibit the pathological process of pulmonary fibrosis. This result provides a new approach for treating pulmonary fibrosis and new insights into the potential application of ZC3H4 in the development of novel therapeutic strategies for mitigating pulmonary fibrosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00761-2. BioMed Central 2022-02-25 /pmc/articles/PMC8881884/ /pubmed/35216634 http://dx.doi.org/10.1186/s13578-022-00761-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yin, Juan Wang, Jing Zhang, Xinxin Liao, Yan Luo, Wei Wang, Sha Ding, Jiawei Huang, Jie Chen, Mengling Wang, Wei Fang, Shencun Chao, Jie A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title | A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title_full | A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title_fullStr | A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title_full_unstemmed | A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title_short | A missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
title_sort | missing piece of the puzzle in pulmonary fibrosis: anoikis resistance promotes fibroblast activation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881884/ https://www.ncbi.nlm.nih.gov/pubmed/35216634 http://dx.doi.org/10.1186/s13578-022-00761-2 |
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