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Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model
BACKGROUND: The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953709/ https://www.ncbi.nlm.nih.gov/pubmed/33711932 http://dx.doi.org/10.1186/s12860-021-00356-8 |
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author | Paw, Milena Wnuk, Dawid Jakieła, Bogdan Bochenek, Grażyna Sładek, Krzysztof Madeja, Zbigniew Michalik, Marta |
author_facet | Paw, Milena Wnuk, Dawid Jakieła, Bogdan Bochenek, Grażyna Sładek, Krzysztof Madeja, Zbigniew Michalik, Marta |
author_sort | Paw, Milena |
collection | PubMed |
description | BACKGROUND: The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β(1) (TGF-β(1)) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepithelial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro, we were interested to see whether corresponding effects could be obtained in a co-culture of the bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β(1) on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. RESULTS: Our results show that the asthmatic co-cultures are more sensitive to the TGF-β(1) than the non-asthmatic ones, which is associated with a higher potential of the asthmatic bronchial cells for a profibrotic response, analogously to be observed in '2D' cultures. They also indicate a noticeable impact of human bronchial epithelial cells on the TGF-β(1)-induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Moreover, our results suggest the protective effects of fibroblasts on the structure of the TGF-β(1)–exposed mucociliary differentiated bronchial epithelial cells and their EMT potential. CONCLUSIONS: Our data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-021-00356-8. |
format | Online Article Text |
id | pubmed-7953709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79537092021-03-12 Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model Paw, Milena Wnuk, Dawid Jakieła, Bogdan Bochenek, Grażyna Sładek, Krzysztof Madeja, Zbigniew Michalik, Marta BMC Mol Cell Biol Research Article BACKGROUND: The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β(1) (TGF-β(1)) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepithelial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro, we were interested to see whether corresponding effects could be obtained in a co-culture of the bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β(1) on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. RESULTS: Our results show that the asthmatic co-cultures are more sensitive to the TGF-β(1) than the non-asthmatic ones, which is associated with a higher potential of the asthmatic bronchial cells for a profibrotic response, analogously to be observed in '2D' cultures. They also indicate a noticeable impact of human bronchial epithelial cells on the TGF-β(1)-induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Moreover, our results suggest the protective effects of fibroblasts on the structure of the TGF-β(1)–exposed mucociliary differentiated bronchial epithelial cells and their EMT potential. CONCLUSIONS: Our data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-021-00356-8. BioMed Central 2021-03-12 /pmc/articles/PMC7953709/ /pubmed/33711932 http://dx.doi.org/10.1186/s12860-021-00356-8 Text en © The Author(s) 2021 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/. The Creative Commons Public Domain Dedication waiver (http://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 Article Paw, Milena Wnuk, Dawid Jakieła, Bogdan Bochenek, Grażyna Sładek, Krzysztof Madeja, Zbigniew Michalik, Marta Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title | Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title_full | Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title_fullStr | Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title_full_unstemmed | Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title_short | Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
title_sort | responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β(1) in epithelial-mesenchymal trophic unit model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953709/ https://www.ncbi.nlm.nih.gov/pubmed/33711932 http://dx.doi.org/10.1186/s12860-021-00356-8 |
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