Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C
Aberrant remodeling of the asthmatic airway is not well understood but is thought to be attributable in part to mechanical compression of airway epithelial cells. Here, we examine compression-induced expression and secretion of the extracellular matrix protein tenascin C (TNC) from well-differentiat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/2/256 |
| _version_ | 1797495214469808128 |
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| author | Chimwemwe Mwase Thien-Khoi N. Phung Michael J. O’Sullivan Jennifer A. Mitchel Margherita De Marzio Ayşe Kılıç Scott T. Weiss Jeffrey J. Fredberg Jin-Ah Park |
| author_facet | Chimwemwe Mwase Thien-Khoi N. Phung Michael J. O’Sullivan Jennifer A. Mitchel Margherita De Marzio Ayşe Kılıç Scott T. Weiss Jeffrey J. Fredberg Jin-Ah Park |
| author_sort | Chimwemwe Mwase |
| collection | DOAJ |
| description | Aberrant remodeling of the asthmatic airway is not well understood but is thought to be attributable in part to mechanical compression of airway epithelial cells. Here, we examine compression-induced expression and secretion of the extracellular matrix protein tenascin C (TNC) from well-differentiated primary human bronchial epithelial (HBE) cells grown in an air–liquid interface culture. We measured <i>TNC</i> mRNA expression using RT-qPCR and secreted TNC protein using Western blotting and ELISA. To determine intracellular signaling pathways, we used specific inhibitors for either ERK or TGF-β receptor, and to assess the release of extracellular vesicles (EVs) we used a commercially available kit and Western blotting. At baseline, secreted TNC protein was significantly higher in asthmatic compared to non-asthmatic cells. In response to mechanical compression, both <i>TNC</i> mRNA expression and secreted TNC protein was significantly increased in both non-asthmatic and asthmatic cells. TNC production depended on both the ERK and TGF-β receptor pathways. Moreover, mechanically compressed HBE cells released EVs that contain TNC. These data reveal a novel mechanism by which mechanical compression, as is caused by bronchospasm, is sufficient to induce the production of ECM protein in the airway and potentially contribute to airway remodeling. |
| first_indexed | 2024-03-10T01:44:37Z |
| format | Article |
| id | doaj.art-c5b049867a8a42c38167ca00b1a8af93 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:44:37Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c5b049867a8a42c38167ca00b1a8af932023-11-23T13:18:33ZengMDPI AGCells2073-44092022-01-0111225610.3390/cells11020256Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin CChimwemwe Mwase0Thien-Khoi N. Phung1Michael J. O’Sullivan2Jennifer A. Mitchel3Margherita De Marzio4Ayşe Kılıç5Scott T. Weiss6Jeffrey J. Fredberg7Jin-Ah Park8Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USAAberrant remodeling of the asthmatic airway is not well understood but is thought to be attributable in part to mechanical compression of airway epithelial cells. Here, we examine compression-induced expression and secretion of the extracellular matrix protein tenascin C (TNC) from well-differentiated primary human bronchial epithelial (HBE) cells grown in an air–liquid interface culture. We measured <i>TNC</i> mRNA expression using RT-qPCR and secreted TNC protein using Western blotting and ELISA. To determine intracellular signaling pathways, we used specific inhibitors for either ERK or TGF-β receptor, and to assess the release of extracellular vesicles (EVs) we used a commercially available kit and Western blotting. At baseline, secreted TNC protein was significantly higher in asthmatic compared to non-asthmatic cells. In response to mechanical compression, both <i>TNC</i> mRNA expression and secreted TNC protein was significantly increased in both non-asthmatic and asthmatic cells. TNC production depended on both the ERK and TGF-β receptor pathways. Moreover, mechanically compressed HBE cells released EVs that contain TNC. These data reveal a novel mechanism by which mechanical compression, as is caused by bronchospasm, is sufficient to induce the production of ECM protein in the airway and potentially contribute to airway remodeling.https://www.mdpi.com/2073-4409/11/2/256asthmaairway remodelingbronchospasmmechanical compressionairway epithelial cellsextracellular matrix |
| spellingShingle | Chimwemwe Mwase Thien-Khoi N. Phung Michael J. O’Sullivan Jennifer A. Mitchel Margherita De Marzio Ayşe Kılıç Scott T. Weiss Jeffrey J. Fredberg Jin-Ah Park Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C Cells asthma airway remodeling bronchospasm mechanical compression airway epithelial cells extracellular matrix |
| title | Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C |
| title_full | Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C |
| title_fullStr | Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C |
| title_full_unstemmed | Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C |
| title_short | Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C |
| title_sort | mechanical compression of human airway epithelial cells induces release of extracellular vesicles containing tenascin c |
| topic | asthma airway remodeling bronchospasm mechanical compression airway epithelial cells extracellular matrix |
| url | https://www.mdpi.com/2073-4409/11/2/256 |
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