S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation

作者全名：Peng, Junnan; Tang, Rui; He, Jing; Yu, Qian; Wang, Daoxin; Qi, Di

作者地址：[Peng, Junnan; Tang, Rui; He, Jing; Yu, Qian; Wang, Daoxin; Qi, Di] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China

通信作者：Qi, D (通讯作者)，Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China.

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001239226100001

JCR分区：Q1

影响因子：6.1

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：S1PR3; ARDS; NF-kappa B; Mitochondrial oxidative phosphorylation; Endothelial cell

摘要：Background Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated.Methods We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS.Results We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-kappa B pathway and improving mitochondrial oxidative phosphorylation.Conclusions S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-kappa B and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

基金机构：National Natural Science Foundation of China; Chongqing Municipal Key Laboratory of Respiratory Inflammation Injury and Precision Medicine, Chongqing, China

基金资助正文：We thank all the members of the research group for their cooperation in the Chongqing Municipal Key Laboratory of Respiratory Inflammation Injury and Precision Medicine, Chongqing, China.