Loss of E-cadherin is causal to pathologic changes in chronic lung disease

• Published in: Communications biology Vol. 5; no. 1; pp. 1149 - 14
• Main Authors: Ghosh, Baishakhi, Loube, Jeffrey, Thapa, Shreeti, Ryan, Hurley, Capodanno, Erin, Chen, Daniel, Swaby, Carter, Chen, Si, Mahmud, Saborny, Girgis, Mirit, Nishida, Kristine, Ying, Linyan, Chengala, Pratulya Pragadaraju, Tieng, Ethan, Burnim, Michael, Wally, Ara, Bhowmik, Debarshi, Zaykaner, Michael, Yeung-Luk, Bonnie, Mitzner, Wayne, Biswal, Shyam, Sidhaye, Venkataramana K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-10-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 14/1; 14/19; 38/109; 38/90; 631/80/79/1902; 692/699/1785/4037; 82/1; 82/29; 82/80; Alveoli; Animal models; Animals; Biology; Biomedical and Life Sciences; Cadherins - genetics; Cadherins - metabolism; Cell culture; Chronic obstructive pulmonary disease; E-cadherin; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Epithelium - metabolism; Life Sciences; Lung - pathology; Lung diseases; Mice; Obstructive lung disease; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Respiratory tract; Therapeutic targets
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-04150-w

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.
Specific loss of the adherens junction protein E-cadherin in alveolar epithelial and airway ciliated cells causes chronic lung disease.