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

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., 5-Sep-2018, In : Scientific Reports. 8, 1, 12 p., 13275.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number13275
Number of pages12
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 5-Sep-2018

    Keywords

  • HOUSE-DUST MITE, AIRWAY EPITHELIUM, BARRIER DYSFUNCTION, RESPIRATORY EPITHELIUM, MESENCHYMAL TRANSITION, ALLERGIC SENSITIZATION, COMPUTED-TOMOGRAPHY, PROGENITOR CELLS, IN-VIVO, ASTHMA

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