Significance of Pyroptosis in Immunoregulation and Prognosis of Patients with Acute Respiratory Distress Syndrome: Evidence from RNA-Seq of Alveolar Macrophages

作者全名："Liu, Bo; Li, Yan; Xiang, Jinying; Li, Yuehan; Zhou, Mi; Ren, Yinying; Fu, Zhou; Ding, Fengxia"

作者地址："[Liu, Bo] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Childrens Hosp,China Int Sci & Technol Cooperat Ba, Chongqing, Peoples R China; [Li, Yan; Xiang, Jinying; Li, Yuehan; Zhou, Mi; Ren, Yinying; Fu, Zhou; Ding, Fengxia] Chongqing Med Univ, Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Li, Yan; Xiang, Jinying; Li, Yuehan; Zhou, Mi; Ren, Yinying; Fu, Zhou; Ding, Fengxia] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Childrens Hosp,China Int Sci & Technol Cooperat Ba, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China"

通信作者："Ding, FX (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Childrens Hosp,China Int Sci & Technol Cooperat Ba, 136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."

来源：JOURNAL OF INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001053614600001

JCR分区：Q2

影响因子：4.2

年份：2023

卷号：16

期号：　

开始页：3547

结束页：3562

文献类型：Article

关键词：ARDS; macrophage; pyroptosis; immune; prognosis

摘要："Objective: This study aimed to investigate the role of pyroptosis in alveolar macrophages regarding the immune microenvironment of acute respiratory distress syndrome (ARDS) and its prognosis. Methods: ARDS Microarray data were downloaded from Gene Expression Omnibus (GEO). Support vector machine (SVM) and random forest (RF) models were applied to identify hub pyroptosis-related genes (PRGs) with prognostic significance in ARDS. RTPCR was used to detect the relative expression of PRGs mRNA in alveolar macrophages of ARDS mice. Consensus clustering analysis was conducted based on the expression of the PRGs to identify pyroptosis modification patterns. Bioinformatic algorithms were used to study the immune traits and biological functions of the pyroptosis patterns. Finally, protein-protein interaction (PPI) networks were established to identify hub regulatory proteins with implications for the pyroptosis patterns.Results: In our study, a total of 12 PRGs with differential expression were obtained. Four hub PRGs, including GPX4, IL6, IL18 and NLRP3, were identified and proven to be predictive of ventilator-free days (VFDS) in ARDS patients. The AUC values of the 4 PRGs were 0.911 (GPX4), 0.879 (IL18), 0.851 (IL6) and 0.841 (NLRP3), respectively. In ARDS mice, GPX4 mRNA decreased significantly, while IL6, IL18, and NLRP3 mRNA increased. Functional analysis revealed that IL6 had the strongest positive correlation with the CCR pathway, while GPX4 exhibited the strongest negative correlation with the T co-inhibition pathway. Based on the expression of the 4 PRGs, three pyroptosis modification patterns representing different immune states were obtained, and pattern C might represent immune storm.Conclusion: The results showed that pyroptosis plays an important regulatory role in the immune microenvironment of ARDS. This finding provides new insights into the pathogenesis, diagnosis, and treatment of ARDS."

基金机构："Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders; [NCRCCHD-2022-YP-05]"

基金资助正文："This study was supported by Scientific Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0930), Project of China Postdoctoral Science Foundation (2022MD713713), Specially Funded Project of Chongqing Postdoctoral Science Foundation (2022CQBSHTB1009), Chongqing Municipal Education Natural Science Foundation (KJQN202200419) and & nbsp;Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders (NCRCCHD-2022-YP-05).r Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders (NCRCCHD-2022-YP-05) ."