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

S. Post, I. H. Heijink*, L. Hesse, H. K. Koo, F. Shaheen, M. Fouadi, V. N. S. Kuchibhotla, B. N. Lambrecht, A. J. M. Van Oosterhout, T. L. Hackett, M. C. Nawijn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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
DOIs
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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