Publication

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

APA

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. (2018). Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology. Scientific Reports, 8(1), [13275]. https://doi.org/10.1038/s41598-018-31500-8

Author

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. / Characterization of a lung epithelium specific E-cadherin knock-out model : Implications for obstructive lung pathology. In: Scientific Reports. 2018 ; Vol. 8, No. 1.

Harvard

Post, S, Heijink, IH, Hesse, L, Koo, HK, Shaheen, F, Fouadi, M, Kuchibhotla, VNS, Lambrecht, BN, Van Oosterhout, AJM, Hackett, TL & Nawijn, MC 2018, 'Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology', Scientific Reports, vol. 8, no. 1, 13275. https://doi.org/10.1038/s41598-018-31500-8

Standard

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.

In: Scientific Reports, Vol. 8, No. 1, 13275, 05.09.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Post S, Heijink IH, Hesse L, Koo HK, Shaheen F, Fouadi M et al. Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology. Scientific Reports. 2018 Sep 5;8(1). 13275. https://doi.org/10.1038/s41598-018-31500-8


BibTeX

@article{c9fc632562b248b880746d561ba0cb51,
title = "Characterization of a lung epithelium specific E-cadherin knock-out model: Implications for obstructive lung pathology",
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.",
keywords = "HOUSE-DUST MITE, AIRWAY EPITHELIUM, BARRIER DYSFUNCTION, RESPIRATORY EPITHELIUM, MESENCHYMAL TRANSITION, ALLERGIC SENSITIZATION, COMPUTED-TOMOGRAPHY, PROGENITOR CELLS, IN-VIVO, ASTHMA",
author = "S. Post and Heijink, {I. H.} and L. Hesse and Koo, {H. K.} and F. Shaheen and M. Fouadi and Kuchibhotla, {V. N. S.} and Lambrecht, {B. N.} and {Van Oosterhout}, {A. J. M.} and Hackett, {T. L.} and Nawijn, {M. C.}",
year = "2018",
month = sep,
day = "5",
doi = "10.1038/s41598-018-31500-8",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Characterization of a lung epithelium specific E-cadherin knock-out model

T2 - Implications for obstructive lung pathology

AU - Post, S.

AU - Heijink, I. H.

AU - Hesse, L.

AU - Koo, H. K.

AU - Shaheen, F.

AU - Fouadi, M.

AU - Kuchibhotla, V. N. S.

AU - Lambrecht, B. N.

AU - Van Oosterhout, A. J. M.

AU - Hackett, T. L.

AU - Nawijn, M. C.

PY - 2018/9/5

Y1 - 2018/9/5

N2 - 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.

AB - 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.

KW - HOUSE-DUST MITE

KW - AIRWAY EPITHELIUM

KW - BARRIER DYSFUNCTION

KW - RESPIRATORY EPITHELIUM

KW - MESENCHYMAL TRANSITION

KW - ALLERGIC SENSITIZATION

KW - COMPUTED-TOMOGRAPHY

KW - PROGENITOR CELLS

KW - IN-VIVO

KW - ASTHMA

U2 - 10.1038/s41598-018-31500-8

DO - 10.1038/s41598-018-31500-8

M3 - Article

C2 - 30185803

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 13275

ER -

ID: 64750109