Transcriptomic analysis of human pulmonary microvascular endothelial cells treated with LPS.

Acute respiratory distress syndrome (ARDS) has a rapid onset and progression, which lead to the severity and complexity of the primary disease and significantly increase the fatality rate of patients. Transcriptomics provides some ideas for clarifying the mechanism of ARDS, exploring prevention and treatment targets, and searching for related specific markers. In this study, RNA-Seq technology was used to observe the gene expression of human pulmonary microvascular endothelial cells (PMVECs) induced by LPS, and to excavate the key genes and signaling pathways in ARDS process. A total of 2300 up-regulated genes were detected, and a corresponding 1696 down-regulated genes were screened. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) were also used for functional annotation of key genes. TFDP1 was identified as a cell cycle-dependent differentially expressed gene, and its reduced expression was verified in LPS-treated PMVECs and lung tissues of CLP-induced mice. In addition, the inhibition of TFDP1 on inflammation and apoptosis, and the promotion of proliferation were confirmed. The decreased expression of E2F1, Rb, CDK1 and the activation of MAPK signaling pathway were substantiated in the in vivo and in vitro models of ARDS. Moreover, SREBF1 has been demonstrated to be involved in cell cycle arrest in PMVECs by inhibiting CDK1. Our study shows that transcriptomics combined with basic research can broaden the investigation of ARDS mechanisms and may provide a basis for future mechanistic innovations.