Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology

• Published in: Scientific reports Vol. 8; no. 1; pp. 13275 - 12
• Main Authors: Post, S., Heijink, I. H., Hesse, L., Koo, H. K., Shaheen, F., Fouadi, M., Kuchibhotla, V. N. S., Lambrecht, B. N., Van Oosterhout, A. J. M., Hackett, T. L., Nawijn, M. C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.09.2018; Nature Publishing Group
• Subjects: 101/1; 13; 13/21; 13/31; 14; 14/28; 38; 38/77; 631/337; 64; 64/60; 692/699/1785/31; 82; 96; Allergens; Alveoli; Asthma; Birth; CCL17 protein; Cell adhesion & migration; Dendritic cells; Denudation; E-cadherin; Epithelial cells; Epithelium; Humanities and Social Sciences; Leukocytes (eosinophilic); Lungs; Metaplasia; Mucous membrane; multidisciplinary; Respiratory tract; Respiratory tract diseases; Science; Science (multidisciplinary); Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31500-8

The airway epithelium regulates responses to aeroallergens, acting as a physical and immunological barrier. In asthma, epithelial barrier function and the expression of adherens junction protein E-cadherin is compromised, but it is unknown whether this is cause or consequence of the disease. We hypothesized that airway epithelial loss of E-cadherin is a critical step in the development of manifestations of asthma. We generated a transgenic mouse model with conditional loss of E-cadherin in lung epithelial cells at birth and onwards. We observed normal lung development at the time of birth in mice lacking E-cadherin in the lung epithelium. However, E-cadherin deficiency led to progressive epithelial damage in mice growing into adulthood, as evidenced by airway epithelial denudation, decreased zonula occludens (ZO)-1 expression, loss of ciliated cells, and enlarged alveolar spaces. In addition, spontaneous goblet cell metaplasia with mucus production was observed. These epithelial changes were accompanied by elevated levels of the epithelial-derived chemokine CCL17, infiltration of eosinophils and dendritic cells, and mucus production. In conclusion, loss of E-cadherin induces features in the lung reminiscent of those observed in asthma, indicating that the disruption of E-cadherin-mediated cell-cell contacts may play a key role in the development of asthma manifestations.