Transcriptome sequencing reveals differential expression of circRNAs in human pulmonary microvascular endothelial cells in acute respiratory distress syndrome

Abstract

Object: To discover the mechanism underlying the role of circulating RNA (circRNA) in pulmonary microvascular permeability in acute respiratory distress syndrome (ARDS). Methods We developed an in vitro model of ARDS using cultured human pulmonary microvascular endothelial cells (HPMECs) and lipopolysaccharide challenge. Genome sequencing showed significant differences among cells in the expression of circRNA. GO and KEGG analysis of target genes were conducted. The circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was constructed. GO enrichment of target genes in the ceRNA network was analyzed. Result Genome sequencing results showed that a total of 379 significantly up-regulated and 448 significantly down-regulated circRNAs. The 10 circRNAs with the greatest degree of up-regulation and the 10 circRNAs with the greatest degree of down-regulation were identified. The results of GO enrichment analysis indicated that differential circRNA expression may mediate the cellular response to DNA damage, including DNA repair. The results of KEGG analysis indicated that the mechanism by which differential circRNA expression exerts these effects may involve the MAPK signaling pathway. GO enrichment analysis of target genes in the ceRNA network showed that the circRNAs were mainly involved in the fluid shear stress response, angiogenesis regulation, vascular development, and cell adhesion. Conclusion Differential expression of circRNAs may play an important role in ARDS, especially in the control of HPMEC permeability. The circRNAs found to have differential expression in response to DNA damage may also be used as biomarkers for early prediction of ARDS disease.