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Related Experiment Video

Updated: Oct 1, 2025

Determining Ciliary Function and Membrane Impermeability of the Pseudostratified Lung Airway Epithelium
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The relation between age and airway epithelial barrier function.

M de Vries1,2, K O Nwozor3,4,5, K Muizer3,4

  • 1University Medical Center Groningen, University of Groningen, Department of Epidemiology, Hanzeplein 1, 9713, Groningen, The Netherlands. m.de.vries04@umcg.nl.

Respiratory Research
|March 4, 2022
PubMed
Summary
This summary is machine-generated.

Aging lungs show impaired epithelial barrier function, linked to specific genes like EPCAM and CDH1. This dysfunction may contribute to age-related airway diseases, impacting respiratory health.

Keywords:
AgeingAirway epithelial cellsCDH1Chronic airway diseasesEPCAMEpithelial barrier function

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Area of Science:

  • Molecular Biology
  • Aging Research
  • Respiratory Medicine

Background:

  • Increasing life expectancy worldwide correlates with a rise in age-associated diseases, including chronic obstructive pulmonary disease (COPD).
  • Previous research identified an aging gene signature in the human lung, highlighting genes involved in apical and tight junction assembly.
  • This suggests a potential role for airway epithelial barrier dysfunction in the aging process.

Purpose of the Study:

  • To investigate the association between genes critical for epithelial barrier function and the aging process.
  • To explore these associations both computationally (in silico) and through laboratory experiments (in vitro) in airway epithelial models.

Main Methods:

  • A curated gene signature of 274 epithelial barrier function genes was analyzed for age association in two independent cohorts of healthy bronchial brushings using linear regression (FDR < 0.05).
  • Protein-protein interactions were mapped using STRING©.
  • In vitro assessments included measuring trans-epithelial resistance (TER) and electric cell-surface impedance sensing (ECIS) in primary bronchial epithelial cells and CRISPR-Cas9 gene-knockdown models (16HBE14o-cells).

Main Results:

  • Fifty-five barrier function genes showed a significant association with age in bronchial brushings (FDR < 0.05).
  • EPCAM expression increased with age, while TRPV4 expression decreased. CDH1 was identified as a potential key regulator negatively associated with age.
  • In vitro studies confirmed reduced barrier function in older individuals' cells (>45 years) and significantly impaired function in CDH1-deficient cells.

Conclusions:

  • A significant link exists between genes regulating epithelial barrier function and chronological age.
  • In vitro functional studies corroborate the in silico findings, demonstrating impaired barrier function.
  • Epithelial barrier dysfunction is suggested as a contributing factor to age-related airway diseases.