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

Author:

Ghosh Baishakhi,Loube Jeffrey,Thapa Shreeti,Ryan Hurley,Capodanno Erin,Chen DanielORCID,Swaby Carter,Chen Si,Mahmud Saborny,Girgis MiritORCID,Nishida Kristine,Ying Linyan,Chengala Pratulya Pragadaraju,Tieng Ethan,Burnim Michael,Wally Ara,Bhowmik Debarshi,Zaykaner Michael,Yeung-Luk Bonnie,Mitzner WayneORCID,Biswal Shyam,Sidhaye Venkataramana K.ORCID

Abstract

AbstractEpithelial 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.

Funder

U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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