Deformation-induced transitional myofibroblasts contribute to compensatory lung growth
In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Physiological Society
2018
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| Online Access: | http://hdl.handle.net/1721.1/119369 https://orcid.org/0000-0001-7014-3830 |
| _version_ | 1826217955688448000 |
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| author | Bennett, Robert D. Ysasi, Alexandra B. Wagner, Willi L. Valenzuela, Cristian D. Tsuda, Akira Pyne, Saumyadipta Li, Shuqiang Grimsby, Jonna Pokharel, Prapti Livak, Kenneth J. Ackermann, Maximilian Mentzer, Steven J. Blainey, Paul C |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Bennett, Robert D. Ysasi, Alexandra B. Wagner, Willi L. Valenzuela, Cristian D. Tsuda, Akira Pyne, Saumyadipta Li, Shuqiang Grimsby, Jonna Pokharel, Prapti Livak, Kenneth J. Ackermann, Maximilian Mentzer, Steven J. Blainey, Paul C |
| author_sort | Bennett, Robert D. |
| collection | MIT |
| description | In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection (P < 0.001). Within 3 days of pneumonectomy, the frequency of SMA⁺ cells in subpleural alveolar ducts was significantly increased (P < 0.01). To determine the functional activity of these SMA⁺ cells, we isolated regenerating alveolar ducts by laser microdissection and analyzed individual cells using microfluidic single-cell quantitative PCR. Single cells expressing the SMA (Acta2) gene demonstrated significantly greater transcriptional activity than endothelial cells or other discrete cell populations in the alveolar duct (P < 0.05). The transcriptional activity of the Acta2⁺ cells, including expression of TGF signaling as well as repair-related genes, suggests that these myofibroblast-like cells contribute to compensatory lung growth. Keywords: compensatory growth; gene expression; lung; myofibroblasts |
| first_indexed | 2024-09-23T17:11:42Z |
| format | Article |
| id | mit-1721.1/119369 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:11:42Z |
| publishDate | 2018 |
| publisher | American Physiological Society |
| record_format | dspace |
| spelling | mit-1721.1/1193692022-10-03T11:04:46Z Deformation-induced transitional myofibroblasts contribute to compensatory lung growth Bennett, Robert D. Ysasi, Alexandra B. Wagner, Willi L. Valenzuela, Cristian D. Tsuda, Akira Pyne, Saumyadipta Li, Shuqiang Grimsby, Jonna Pokharel, Prapti Livak, Kenneth J. Ackermann, Maximilian Mentzer, Steven J. Blainey, Paul C Massachusetts Institute of Technology. Department of Biological Engineering Blainey, Paul C Blainey, Paul C In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection (P < 0.001). Within 3 days of pneumonectomy, the frequency of SMA⁺ cells in subpleural alveolar ducts was significantly increased (P < 0.01). To determine the functional activity of these SMA⁺ cells, we isolated regenerating alveolar ducts by laser microdissection and analyzed individual cells using microfluidic single-cell quantitative PCR. Single cells expressing the SMA (Acta2) gene demonstrated significantly greater transcriptional activity than endothelial cells or other discrete cell populations in the alveolar duct (P < 0.05). The transcriptional activity of the Acta2⁺ cells, including expression of TGF signaling as well as repair-related genes, suggests that these myofibroblast-like cells contribute to compensatory lung growth. Keywords: compensatory growth; gene expression; lung; myofibroblasts National Institutes of Health (U.S.) (Grant HL94567) National Institutes of Health (U.S.) (Grant CA009535) National Institutes of Health (U.S.) (Grant ES000002) 2018-11-29T16:30:50Z 2018-11-29T16:30:50Z 2017-01 2016-08 Article http://purl.org/eprint/type/JournalArticle 1040-0605 1522-1504 http://hdl.handle.net/1721.1/119369 Bennett, Robert D. et al. “Deformation-Induced Transitional Myofibroblasts Contribute to Compensatory Lung Growth.” American Journal of Physiology-Lung Cellular and Molecular Physiology 312, 1 (January 2017): L79–L88 © 2017 American Physiological Society https://orcid.org/0000-0001-7014-3830 en_US https://doi.org/10.1152/ajplung.00383.2016 American Journal of Physiology-Lung Cellular and Molecular Physiology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Physiological Society Prof. Blainey via Howard Silver |
| spellingShingle | Bennett, Robert D. Ysasi, Alexandra B. Wagner, Willi L. Valenzuela, Cristian D. Tsuda, Akira Pyne, Saumyadipta Li, Shuqiang Grimsby, Jonna Pokharel, Prapti Livak, Kenneth J. Ackermann, Maximilian Mentzer, Steven J. Blainey, Paul C Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title | Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title_full | Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title_fullStr | Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title_full_unstemmed | Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title_short | Deformation-induced transitional myofibroblasts contribute to compensatory lung growth |
| title_sort | deformation induced transitional myofibroblasts contribute to compensatory lung growth |
| url | http://hdl.handle.net/1721.1/119369 https://orcid.org/0000-0001-7014-3830 |
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