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Updated: Feb 18, 2026
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
Novel mechanisms for crotonaldehyde-induced lung edema
Yue Li1, Jianjun Chang1, Yong Cui2
1Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110122, Liaoning, China.
Background:
Crotonaldehyde is a highly noxious α,β-unsaturated aldehyde in cigarette smoke that causes edematous acute lung injury.
Objective:
To understand how crotonaldehyde impairs lung function, we examined its effects on human epithelial sodium channels (ENaC), which are major contributors to alveolar fluid clearance.
Methods:
We studied alveolar fluid clearance in C57 mice and ENaC activity was examined in H441 cells. Expression of α- and γ-ENaC was measured at protein and mRNA levels by western blot and real-time PCR, respectively. Intracellular ROS levels were detected by the dichlorofluorescein assay. Heterologous αβγ-ENaC activity was observed in an oocyte model.
Results:
Our results showed that crotonaldehyde reduced transalveolar fluid clearance in mice. Furthermore, ENaC activity in H441 cells was inhibited by crotonaldehyde dose-dependently. Expression of α- and γ-subunits of ENaC was decreased at the protein and mRNA level in H441 cells exposed to crotonaldehyde, which was probably mediated by the increase in phosphorylated extracellular signal-regulated protein kinases 1 and 2. ROS levels increased time-dependently in cells exposed to crotonaldehyde. Heterologous αβγ-ENaC activity was rapidly eliminated by crotonaldehyde.
Conclusion:
Our findings suggest that crotonaldehyde causes edematous acute lung injury by eliminating ENaC activity at least partly via facilitating the phosphorylation of extracellular signal-regulated protein kinases 1 and 2 signal molecules. Long-term exposure may decrease the expression of ENaC subunits and damage the cell membrane integrity, as well as increase the levels of cellular ROS products.
