TY - JOUR
T1 - Loss of E-cadherin is causal to pathologic changes in chronic lung disease
AU - Ghosh, Baishakhi
AU - Loube, Jeffrey
AU - Thapa, Shreeti
AU - Ryan, Hurley
AU - Capodanno, Erin
AU - Chen, Daniel
AU - Swaby, Carter
AU - Chen, Si
AU - Mahmud, Saborny
AU - Girgis, Mirit
AU - Nishida, Kristine
AU - Ying, Linyan
AU - Chengala, Pratulya Pragadaraju
AU - Tieng, Ethan
AU - Burnim, Michael
AU - Wally, Ara
AU - Bhowmik, Debarshi
AU - Zaykaner, Michael
AU - Yeung-Luk, Bonnie
AU - Mitzner, Wayne
AU - Biswal, Shyam
AU - Sidhaye, Venkataramana K.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Epithelial cells line the lung mucosal surface and are the first line of defense against toxic exposures to environmental insults, and their integrity is critical to lung health. An early finding in the lung epithelium of patients with chronic obstructive pulmonary disease (COPD) is the loss of a key component of the adherens junction protein called E-cadherin. The cause of this decrease is not known and could be due to luminal insults or structural changes in the small airways. Irrespective, it is unknown whether the loss of E-cadherin is a marker or a driver of disease. Here we report that loss of E-cadherin is causal to the development of chronic lung disease. Using cell-type-specific promoters, we find that knockout of E-cadherin in alveolar epithelial type II but not type 1 cells in adult mouse models results in airspace enlargement. Furthermore, the knockout of E-cadherin in airway ciliated cells, but not club cells, increase airway hyperreactivity. We demonstrate that strategies to upregulate E-cadherin rescue monolayer integrity and serve as a potential therapeutic target.
AB - Epithelial cells line the lung mucosal surface and are the first line of defense against toxic exposures to environmental insults, and their integrity is critical to lung health. An early finding in the lung epithelium of patients with chronic obstructive pulmonary disease (COPD) is the loss of a key component of the adherens junction protein called E-cadherin. The cause of this decrease is not known and could be due to luminal insults or structural changes in the small airways. Irrespective, it is unknown whether the loss of E-cadherin is a marker or a driver of disease. Here we report that loss of E-cadherin is causal to the development of chronic lung disease. Using cell-type-specific promoters, we find that knockout of E-cadherin in alveolar epithelial type II but not type 1 cells in adult mouse models results in airspace enlargement. Furthermore, the knockout of E-cadherin in airway ciliated cells, but not club cells, increase airway hyperreactivity. We demonstrate that strategies to upregulate E-cadherin rescue monolayer integrity and serve as a potential therapeutic target.
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U2 - 10.1038/s42003-022-04150-w
DO - 10.1038/s42003-022-04150-w
M3 - Article
C2 - 36309587
AN - SCOPUS:85140908403
SN - 2399-3642
VL - 5
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 1149
ER -