Transcriptomic analysis of human pulmonary microvascular endothelial cells treated with LPS

Kaili Li; Zuotian Huang; Chang Liu; Yuanyuan Xu; Wei Chen; Lu Shi; Can Li; Fawei Zhou; Fachun Zhou

doi:10.1016/j.cellsig.2023.110870

Transcriptomic analysis of human pulmonary microvascular endothelial cells treated with LPS

Cell Signal. 2023 Nov:111:110870. doi: 10.1016/j.cellsig.2023.110870. Epub 2023 Aug 25.

Authors

Kaili Li¹, Zuotian Huang², Chang Liu³, Yuanyuan Xu⁴, Wei Chen⁴, Lu Shi⁴, Can Li⁴, Fawei Zhou⁴, Fachun Zhou⁵

Affiliations

¹ Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China. Electronic address: 2019110257@stu.cqmu.edu.cn.
² Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, 400030 Chongqing Municipality, China.
³ Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China. Electronic address: liuchangccm@hospital.cqmu.edu.cn.
⁴ Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
⁵ Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China; Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China. Electronic address: cyzfc1966@126.com.

PMID: 37633475
DOI: 10.1016/j.cellsig.2023.110870

Abstract

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.

Keywords: Acute respiratory distress syndrome; Human pulmonary microvascular endothelial cells; SREBF1; TFDP1; Transcriptomics.