ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1637378
This article is part of the Research TopicExploring the Biology of Inflammasomes: Mechanisms, Disorders, and Therapeutic PotentialView all 3 articles
Low-Dose Extracorporeal Shock Wave Attenuates Sepsis-Related Acute Lung Injury by Targeting Mitochondrial Dysfunction and Pyroptosis Crosstalk in Type II Alveolar Epithelial Cells
Provisionally accepted
Jianning Guo
Xiaoxuan Qu
Ruidong Ge
Die Liu
Jing Liu
Hui Qin
Fang YeYuanmei Chen
chao wang
Di LvLijuan TangMeihong Xia
Qi Zhang*- China-Japan Friendship Hospital, Beijing, China
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The pathological mechanism of sepsis-related acute lung injury (ALI) is closely linked to mitochondrial dysfunction and pyroptosis. Although low-dose extracorporeal shock wave (SW) therapy has been widely utilized in tissue and organ injury repair, its role in sepsis-related ALI remains unclear. This study aimed to elucidate the regulatory mechanisms of SW on mitochondrial pyroptosis crosstalk in septic ALI.: The sepsis-related ALI mouse model was induced by tail vein injection of LPS. In vitro, LPS and ATP induced a pyroptosis model in type II alveolar epithelial (AT2) cells. The levels of inflammatory factors and oxidative stress were detected. The ultrastructure of lung mitochondria was observed by transmission electron microscope. Moreover, the mitochondrial membrane potential, ATP content, and the level of mtDNA were determined in cells and tissues. Western blot was used to detect mitochondrial oxidative stress and dysfunction, as well as the expression of pyroptosis-related proteins mediated by NLRP3 inflammasome. Results: SW significantly reduced the secretion levels of inflammatory factors TNF-α, IL-1β, IL-6, and IL-8 in serum, alveolar lavage fluid (BALF), and cell supernatant, inhibited oxidative stress markers (ROS, MDA, MPO), and upregulated antioxidant index (SOD, GSH). Pathological evidence indicates that SW can alleviate the pathological changes of lung injury and restore the mitochondrial ultrastructure of AT2 cells. The mechanism study shows that SW can enhance mitochondrial membrane potential and ATP production, inhibit mtDNA migration and p65 nuclear translocation, and down-regulate the expression of mitochondrial coding genes (MT-ND2, MT-ND4) and iNOS. At the same time, SW inhibited the NLRP3/ASC/Caspase-1 signaling axis, thereby disrupting pyroptosis cascades.This study reveals that SW attenuates septic ALI by targeting mitochondrial-pyroptosis crosstalk, offering a novel non-invasive therapeutic strategy for clinical applications.
Keywords: shock wave, Sepsis, Acute Lung Injury, Type II alveolar epithelial cell, mitochondrial DNA, pyroptosis
Received: 29 May 2025; Accepted: 01 Aug 2025.
Copyright: © 2025 Guo, Qu, Ge, Liu, Liu, Qin, Ye, Chen, wang, Lv, Tang, Xia and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qi Zhang, China-Japan Friendship Hospital, Beijing, China
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