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Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation

Goodwin, Amanda T.; John, Alison E.; Joseph, Chitra; Habgood, Anthony; Tatler, Amanda L.; Susztak, Katalin; Palmer, Matthew; Offermanns, Stefan; Henderson, Neil C.; Jenkins, R. Gisli

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Clinical Assistant Professor (Nihr Clinical Lecturer in Respiratory Medicine)

Alison E. John

Anthony Habgood

Principal Research Fellow

Katalin Susztak

Matthew Palmer

Stefan Offermanns

Neil C. Henderson

R. Gisli Jenkins


Alveolar development and repair require tight spatiotemporal regulation of numerous signalling pathways that are influenced by chemical and mechanical stimuli. Mesenchymal cells play key roles in numerous developmental processes. Transforming growth factor-β (TGFβ) is essential for alveologenesis and lung repair, and the G protein α subunits Gαq and Gα11 (Gαq/11) transmit mechanical and chemical signals to activate TGFβ in epithelial cells. To understand the role of mesenchymal Gαq/11 in lung development, we generated constitutive (Pdgfrb-Cre+/-;Gnaqfl/fl;Gna11-/-) and inducible (Pdgfrb-Cre/ERT2+/-;Gnaqfl/fl;Gna11-/-) mesenchymal Gαq/11 deleted mice. Mice with constitutive Gαq/11 gene deletion exhibited abnormal alveolar development, with suppressed myofibroblast differentiation, altered mesenchymal cell synthetic function, and reduced lung TGFβ2 deposition, as well as kidney abnormalities. Tamoxifen-induced mesenchymal Gαq/11 gene deletion in adult mice resulted in emphysema associated with reduced TGFβ2 and elastin deposition. Cyclical mechanical stretch-induced TGFβ activation required Gαq/11 signalling and serine protease activity, but was independent of integrins, suggesting an isoform-specific role for TGFβ2 in this model. These data highlight a previously undescribed mechanism of cyclical stretch-induced Gαq/11-dependent TGFβ2 signalling in mesenchymal cells, which is imperative for normal alveologenesis and maintenance of lung homeostasis.


Goodwin, A. T., John, A. E., Joseph, C., Habgood, A., Tatler, A. L., Susztak, K., …Jenkins, R. G. (2023). Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation. Development, 150(9),

Journal Article Type Article
Acceptance Date Apr 5, 2023
Online Publication Date Apr 27, 2023
Publication Date May 1, 2023
Deposit Date May 6, 2023
Publicly Available Date May 11, 2023
Journal Development
Print ISSN 0950-1991
Electronic ISSN 1477-9129
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 150
Issue 9
Keywords Alveologenesis, TGFβ, Gαq/11, GPCR, Lung development, Cyclical mechanical stretch
Public URL
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Additional Information © 2023. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed


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