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Sci Rep. 2020 Jan 22;10(1):966. doi: 10.1038/s41598-020-57755-8.

Mechanical forces induce an asthma gene signature in healthy airway epithelial cells.

Author information

1
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
2
Department of Physics, Northeastern University, Boston, MA, USA.
3
Program in Molecular Integrative Phyisological Sciences, Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA.
4
Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
5
Centre for Research and Interdisciplinarity (CRI), Paris, F-75014, France.
6
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
7
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
8
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, 44106, USA.
9
Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina, Chapel Hill, NC, USA.
10
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. scott.weiss@channing.harvard.edu.
11
Program in Molecular Integrative Phyisological Sciences, Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA. scott.weiss@channing.harvard.edu.

Abstract

Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufficient to induce inflammatory, late repair, and fibrotic pathways. Remarkably, this molecular profile of non-asthmatic cells after compression recapitulated the profile of asthmatic cells before compression. Together, these results show that even in the absence of any inflammatory stimulus, mechanical compression alone is sufficient to induce an asthma-like molecular signature.

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