Fenvalerate Induces Airway Epithelial Injury Through CHRM3-Associated NF-κB Activation
- 1College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
Abstract
Fenvalerate (FEN) is a widely used pyrethroid insecticide with potential respiratory toxicity; however, its contribution to chronic obstructive pulmonary disease (COPD)-related pathological processes remains unclear. We investigated molecular mechanisms linking FEN exposure to airway epithelial injury. COPD transcriptomic datasets were integrated with predicted FEN targets, and candidate genes were prioritized using machine-learning algorithms. Immune infiltration and single-cell transcriptomic analyses were used to examine immune associations and cell-type-specific expression. Molecular docking and molecular dynamics simulations assessed potential FEN-target interactions, followed by validation in BEAS-2B human bronchial epithelial cells. Intersecting FEN-COPD genes were enriched in inflammatory, immune-regulatory, neuroactive ligand-receptor, and epithelial injury-related pathways. Eight candidate genes showed distinct expression patterns across airway epithelial and immune cell populations. Computational analyses supported a potentially stable FEN-CHRM3 interaction. In BEAS-2B cells, FEN reduced viability, increased IL-6 and IL-8 secretion, promoted apoptosis, upregulated CHRM3, and enhanced IκBα and p65 phosphorylation. Pharmacological inhibition of CHRM3 or NF-κB partially attenuated these responses. Thus, FEN-induced epithelial inflammation and apoptosis may involve CHRM3-associated NF-κB activation, providing mechanistic insight into pesticide-related respiratory toxicity.
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BibTeX
@article{yang2026fenvalerate,
title = {{Fenvalerate Induces Airway Epithelial Injury Through CHRM3-Associated NF-κB Activation}},
author = {Yuxin Yang and Jixin Li and Tong Liu and Mingyang Sheng and Jiatong Liu and Zidong Yang and Hongbo Chu and Ailing Jia and Wei Xu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209201},
url = {https://www.mdpi.com/1422-0067/27/20/9201},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fenvalerate Induces Airway Epithelial Injury Through CHRM3-Associated NF-κB Activation
AU - Yuxin Yang
AU - Jixin Li
AU - Tong Liu
AU - Mingyang Sheng
AU - Jiatong Liu
AU - Zidong Yang
AU - Hongbo Chu
AU - Ailing Jia
AU - Wei Xu
PY - 2026
DA - 2026/10/16
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209201
UR - https://www.mdpi.com/1422-0067/27/20/9201
AB - Fenvalerate (FEN) is a widely used pyrethroid insecticide with potential respiratory toxicity; however, its contribution to chronic obstructive pulmonary disease (COPD)-related pathological processes remains unclear. We investigated molecular mechanisms linking FEN exposure to airway epithelial injury. COPD transcriptomic datasets were integrated with predicted FEN targets, and candidate genes were prioritized using machine-learning algorithms. Immune infiltration and single-cell transcriptomic analyses were used to examine immune associations and cell-type-specific expression. Molecular docking and molecular dynamics simulations assessed potential FEN-target interactions, followed by validation in BEAS-2B human bronchial epithelial cells. Intersecting FEN-COPD genes were enriched in inflammatory, immune-regulatory, neuroactive ligand-receptor, and epithelial injury-related pathways. Eight candidate genes showed distinct expression patterns across airway epithelial and immune cell populations. Computational analyses supported a potentially stable FEN-CHRM3 interaction. In BEAS-2B cells, FEN reduced viability, increased IL-6 and IL-8 secretion, promoted apoptosis, upregulated CHRM3, and enhanced IκBα and p65 phosphorylation. Pharmacological inhibition of CHRM3 or NF-κB partially attenuated these responses. Thus, FEN-induced epithelial inflammation and apoptosis may involve CHRM3-associated NF-κB activation, providing mechanistic insight into pesticide-related respiratory toxicity.
SN - 1422-0067
ER -