单位：[a]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China[b]Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P. R. China[c]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China[d]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China[e]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China[f]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China
Purpose: The proteome during lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice is unclear. Materials and Methods: In this study, eight-week-old male C57BL/6 mice were intraperitoneally injected with LPS and sacrificed 18 hours after LPS administration to identify protein expression levels in lung tissue using tandem mass tag (TMT) analysis for relative quantification. Hematoxylin-eosin (HE) staining was used to evaluate lung injury in mice. Immunohistochemical staining was used to calculate the production of myeloperoxidase (MPO) and TUNEL staining was performed to detect apoptosis. GO functional clustering and KEGG pathway enrichment analyses were performed to determine functions of differentially expressed proteins (DEPs) and transduction pathways. Domain annotation and subcellular localization analysis of the DEPs were also performed. Furthermore, parallel reaction monitoring (PRM) analysis was used to verify the top 30 DEPs. Results: A total of 5188 proteins were found to be expressed in lung tissues from LPS- and saline-treated mice. Among these proteins, 293 were differentially expressed between the two groups; 255 proteins were upregulated in the LPS-treated ALI mice, while 38 were downregulated. GO analysis showed that the DEPs are mainly extracellular, and KEGG analysis suggested that the DEPs are mainly enriched in the NOD-like receptor signaling pathway, complement and coagulation cascades and natural killer cell-mediated cytotoxicity. Enrichment of the DEPs is mainly peptidase S1A, serine proteases, peptidase S1, and the serpin domain. 26.6% of the DEPs are in the nucleus, 24.6% are in the cytosol, 19.1% are in the extracellular space, and 18.8% are in the plasma membrane. PRM validation showed that the trend of 30 DEPs was same with TMT analysis. Among these, Cytochrome b-245 heavy chain (Cybb), Monocyte differentiation antigen CD14 (Cd14) and Neutrophil gelatinase-associated lipocalin (NGAL) were the most obvious change. Conclusions: Our results may help to identify markers and therapeutic targets for LPS-induced ALI.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81870072]
第一作者单位：[a]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China[b]Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P. R. China[c]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China[d]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China[e]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China[f]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China
通讯作者：
通讯机构：[a]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China[c]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China[d]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China[e]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China[f]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China[*1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, Beijing 100029, P. R. China
