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Stretch increases alveolar type 1 cell number in fetal lungs through ROCK-Yap/Taz pathway

Nguyen, Tram Mai ; van der Merwe, Johannes ; Elowsson Rendin, Linda LU ; Larsson-Callerfelt, Anna Karin LU orcid ; Deprest, Jan ; Westergren-Thorsson, Gunilla LU and Toelen, Jaan (2021) In American journal of physiology. Lung cellular and molecular physiology 321(5). p.814-826
Abstract

Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that... (More)

Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that stretch-induced Yap/Taz activation promotes alveolar differentiation toward AT1 phenotype via ROCK activity. Our findings show that balanced ROCK-Yap/Taz signaling is essential to regulate AT1 differentiation in response to mechanical stretching of the fetal lung, which might be helpful in improving lung development and regeneration.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alveolar cell type 1, lung mechanotransduction, ROCK pathway, tracheal occlusion, Yap/Taz
in
American journal of physiology. Lung cellular and molecular physiology
volume
321
issue
5
pages
814 - 826
publisher
American Physiological Society
external identifiers
  • scopus:85120508294
  • pmid:34431413
ISSN
1522-1504
DOI
10.1152/ajplung.00484.2020
language
English
LU publication?
yes
id
40a090dd-cf3d-442a-820e-a540a262b655
date added to LUP
2022-01-18 17:19:29
date last changed
2024-04-20 20:09:41
@article{40a090dd-cf3d-442a-820e-a540a262b655,
  abstract     = {{<p>Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that stretch-induced Yap/Taz activation promotes alveolar differentiation toward AT1 phenotype via ROCK activity. Our findings show that balanced ROCK-Yap/Taz signaling is essential to regulate AT1 differentiation in response to mechanical stretching of the fetal lung, which might be helpful in improving lung development and regeneration.</p>}},
  author       = {{Nguyen, Tram Mai and van der Merwe, Johannes and Elowsson Rendin, Linda and Larsson-Callerfelt, Anna Karin and Deprest, Jan and Westergren-Thorsson, Gunilla and Toelen, Jaan}},
  issn         = {{1522-1504}},
  keywords     = {{alveolar cell type 1; lung mechanotransduction; ROCK pathway; tracheal occlusion; Yap/Taz}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{814--826}},
  publisher    = {{American Physiological Society}},
  series       = {{American journal of physiology. Lung cellular and molecular physiology}},
  title        = {{Stretch increases alveolar type 1 cell number in fetal lungs through ROCK-Yap/Taz pathway}},
  url          = {{http://dx.doi.org/10.1152/ajplung.00484.2020}},
  doi          = {{10.1152/ajplung.00484.2020}},
  volume       = {{321}},
  year         = {{2021}},
}