The integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in alcohol induced ARDS
- 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University
- 2Key Laboratory of Respiratory Inflammatory Injury and Precision Diagnosis and Treatment, Chongqing Municipal Health and Health Committee
- 3Chongqing Key Laboratory of Precision Medicine and Prevention of Major Respiratory Diseases
Abstract
Introduction: Acute respiratory distress syndrome (ARDS) is characterized by impaired alveolar-capillary permeability and pulmonary edema. Alveolar fluid clearance (AFC) is strongly associated with patient prognosis. This study aimed to investigate whether chronic alcohol consumption affects sodium channel regulation in ARDS via the Integrin αvβ6/TGF-β1/Smad4 signaling pathway.
Methods: We established chronic alcohol exposure models in mice and MLE-12 cells, followed by lipopolysaccharide (LPS)-induced ARDS in both systems. The Integrin αvβ6/TGF-β1/Smad4 pathway was inhibited to explore its regulatory effect on ENaC and Na ⁺ ,K ⁺ -ATPase during alcohol-induced ARDS.
Results: We found that chronic alcohol consumption exacerbated lung injury by activating this signaling pathway, which suppressed ENaC and Na ⁺ ,K ⁺ -ATPase protein expression. Inhibition of the pathway alleviated pulmonary edema and inflammation and improved survival rates. Both in vivo and in vitro results demonstrated that the Integrin αvβ6/TGF-β1/Smad4 pathway regulates ENaC and Na ⁺ ,K ⁺ -ATPase in alcohol-induced ARDS.
Conclusion: These findings may clarify the regulatory mechanisms of sodium channels in ARDS associated with chronic alcohol consumption.
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BibTeX
@article{dai2026integrin,
title = {{The integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in alcohol induced ARDS}},
author = {Xue Dai and Xue-Ling Liu and Mei-Jun Liu and Ting Li and Dao-Xin Wang and Wang Deng},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1931568},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1931568/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in alcohol induced ARDS
AU - Xue Dai
AU - Xue-Ling Liu
AU - Mei-Jun Liu
AU - Ting Li
AU - Dao-Xin Wang
AU - Wang Deng
PY - 2026
DA - 2026/10/16
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1931568
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1931568/full
AB - Introduction: Acute respiratory distress syndrome (ARDS) is characterized by impaired alveolar-capillary permeability and pulmonary edema. Alveolar fluid clearance (AFC) is strongly associated with patient prognosis. This study aimed to investigate whether chronic alcohol consumption affects sodium channel regulation in ARDS via the Integrin αvβ6/TGF-β1/Smad4 signaling pathway. Methods: We established chronic alcohol exposure models in mice and MLE-12 cells, followed by lipopolysaccharide (LPS)-induced ARDS in both systems. The Integrin αvβ6/TGF-β1/Smad4 pathway was inhibited to explore its regulatory effect on ENaC and Na ⁺ ,K ⁺ -ATPase during alcohol-induced ARDS. Results: We found that chronic alcohol consumption exacerbated lung injury by activating this signaling pathway, which suppressed ENaC and Na ⁺ ,K ⁺ -ATPase protein expression. Inhibition of the pathway alleviated pulmonary edema and inflammation and improved survival rates. Both in vivo and in vitro results demonstrated that the Integrin αvβ6/TGF-β1/Smad4 pathway regulates ENaC and Na ⁺ ,K ⁺ -ATPase in alcohol-induced ARDS. Conclusion: These findings may clarify the regulatory mechanisms of sodium channels in ARDS associated with chronic alcohol consumption.
SN - 1663-9812
ER -