Electronic cigarette aerosols alter the respiratory tract barrier

Electronic cigarettes are growing in popularity, but their effects on respiratory health remain poorly understood. Recent research reveals that inhaled aerosols disrupt the integrity of the respiratory epithelium, an essential barrier that protects the lungs from harmful particles and microbes. This disruption is based on a specific mechanism: the degradation of E-cadherin, a key protein that maintains cohesion between epithelial cells.

E-cadherin can be cleaved by enzymes called matrix metalloproteinases, releasing a soluble form, sE-cadherin. The latter weakens the epithelial barrier and promotes inflammation. Scientists have observed that exposure to electronic cigarette aerosols increases the production of sE-cadherin in human bronchial cells and in mice. At the same time, the expression of three metalloproteinases—MMP-2, MMP-9, and MMP-12—is stimulated, confirming their role in this process.

The consequences are direct: transepithelial electrical resistance, an indicator of barrier tightness, decreases sharply after exposure to aerosols. Additionally, permeability to molecules such as labeled dextran increases, proving that the barrier becomes more permeable and less protective. Images obtained by microscopy also show disorganization of junction proteins, such as ZO-1 and occludin, which normally ensure tightness between cells.

To confirm the link between metalloproteinases and this damage, researchers used fisetin, a natural inhibitor of these enzymes. Treatment with fisetin significantly reduces the release of sE-cadherin and preserves the structure of cellular junctions. It also mitigates the decrease in electrical resistance and limits the increase in permeability. These results highlight that MMP-9 plays a central role in the degradation of E-cadherin, as its expression is specifically reduced by fisetin, unlike the other metalloproteinases.

These findings show that electronic cigarette aerosols compromise the epithelial barrier by activating enzymes that degrade cellular cohesion proteins. sE-cadherin, which is easy to detect in biological fluids, could thus serve as an early marker to assess the damage caused by vaping. Furthermore, targeting metalloproteinases, particularly MMP-9, opens avenues for developing treatments to protect the respiratory tract from the harmful effects of aerosols.

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Official Study Source

DOI: https://doi.org/10.1007/s00204-026-04456-2

Title: Electronic cigarette aerosols disrupt airway barrier function via MMP-dependent E-cadherin cleavage: findings from cell culture and murine models

Journal: Archives of Toxicology

Publisher: Springer Science and Business Media LLC

Authors: Amelia L. Beaumont; Sarah G. Ozeki; Claire E. Lee; Robert L. Chatburn; Russell P. Bowler; Fariba Rezaee