Analysis of Long Noncoding RNA Expression Profile in Human Pulmonary Microvascular Endothelial Cells Exposed to Lipopolysaccharide

Abstract

Background/aims: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a continuum of life-threatening lung changes. Pulmonary vascular injury is one of the most important initial causes of ALI and ARDS. However, the functions of long noncoding RNAs (lncRNAs) in pulmonary endothelial injury remain largely unknown. The aim of the present study was to determine the lncRNA expression profile of human pulmonary microvascular endothelial cells (HPMECs) exposed to lipopolysaccharide (LPS) and explore the potential functions of differentially expressed lncRNAs.

Methods: Microarray analysis was used to identify differentially expressed lncRNAs and mRNAs. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, lncRNA-mRNA coexpression network and transcription factor (TF)-lncRNA network analyses, were performed to predict the functions of significantly differentially expressed lncRNAs and mRNAs. Realtime polymerase chain reaction (PCR) was used to determine the expression of selected lncRNAs and mRNAs.

Results: In this study, we found that 213 lncRNAs and 212 mRNAs were significantly differentially expressed in HPMECs exposed to LPS (fold change > 2.0, p < 0.05). Furthermore, we found that mRNAs co-expressed with lncRNAs were significantly enriched in the TNF signaling pathway, the NF-κB signaling pathway, cell adhesion molecules (CAMs), cytokine-cytokine receptor interactions, and extracellular matrix (ECM)-receptor interactions. The expression levels of all but one of the selected lncRNAs and mRNAs detected by real-time PCR were similar to those detected by microarray analysis.

Conclusion: Our data indicate that lncRNAs play an important role in LPS-induced pulmonary endothelial inflammation and barrier dysfunction and may be potential preventive and therapeutic targets for ALI and ARDS.

Keywords: Acute lung injury; Expression profile; Human pulmonary microvascular endothelial cell; Lipopolysaccharide; Long noncoding RNA.