ASIC1a regulates airway epithelial cell pyroptosis in acute lung injury by NLRP3-Caspase1-GSDMD pathway.

Autor: Tan YY; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China., Zhang DW; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China., Yang C; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China; Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Huang Y; School of Pharmacy, Anhui Medical University, Hefei, China., Kang JY; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China., Xu ZH; Center for Scientific Research, The First Affiliated Hospital of Anhui Medical University, Hefei, China., Wei YY; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China., Ding ZX; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China; Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: dingzhenxing@ahmu.edu.cn., Fei GH; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China; Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei 230022, Anhui Province, China. Electronic address: gh.fei@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 3), pp. 113623. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1016/j.intimp.2024.113623
Abstrakt: Background: Acidosis is the most common complication that seriously affects the prognosis of acute respiratory distress syndrome (ARDS). Acid-sensitive ion channel 1a (ASIC1a) is activated in acidic environments to regulate inflammatory process. However, the role of ASIC1a in ARDS is unclear.
Methods: In this study, we examined the expression of ASIC1a in airway epithelial cells in an acidic environment. We then investigated whether blocking ASIC1a could inhibit pyroptosis of airway epithelial cells and the molecular mechanism. In the mouse acute lung injury (ALI) model, we observed the changes of lung histopathology, arterial blood gas and pyroptosis related indexes after ASIC1a inhibition. Bronchoalveolar lavage fluid (BALF) from patients with ARDS were collected to explore the expression level of ASIC1a in ARDS patients.
Results: Inhibiting ASIC1a can reduce the airway epithelial cell pyroptosis induced by an extracellular acidic environment. ASIC1a can bind to PRKACA, and silencing ASIC1a and PRKACA can inhibit the occurrence of pyroptosis in airway epithelial cells. Compared with control group, arterial blood pH and PaO 2 in ALI group were significantly reduced. The inflammation in the lungs is more intense, and the mRNA and protein of NLRP3, Caspase1 and GSDMD were increased, while ASIC1a specific blocker psalmotoxin-1 alleviated this phenomenon. The expression of ASIC1a in BALF of ARDS patients was significantly increased, especially in non-survival group.
Conclusion: Acidic micro-environment can induce the increased expression of ASIC1a, and inhibition of ASIC1a can alleviate the inflammation and airway epithelial cell pyroptosis in ARDS. ASIC1a may be a new target for the treatment of ARDS.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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