Wang Nan, Gao Yongheng, Xue Peini, Surani Salim, Schwartz Gary S, Ma Ruina, Li Yanyan, Liu Wei
Department of Respiratory, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.
Graduate Faculty, Xi'an Medical University, Xi'an, China.
J Thorac Dis. 2025 Jun 30;17(6):4104-4116. doi: 10.21037/jtd-2025-1038. Epub 2025 Jun 26.
Acute respiratory distress syndrome (ARDS) is characterized by elevated pulmonary microvascular permeability; however, the role of circular RNAs (circRNAs) in this process remains unclear. Our study aims to discover the mechanism underlying the role of circRNA in pulmonary microvascular permeability in ARDS.
We developed an model of ARDS using cultured human pulmonary microvascular endothelial cells (HPMECs) and lipopolysaccharide challenge. Genome sequencing revealed significant differences among the cells in the expression of circRNA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the target genes were conducted. A circRNA-microRNA (miRNA)-messenger RNA (mRNA) competitive endogenous RNA (ceRNA) network was constructed. The GO enrichment analysis of the target genes in the ceRNA network was analyzed.
The genome sequencing results identified 379 significantly upregulated circRNAs and 448 significantly downregulated circRNAs. The 10 circRNAs with the greatest degree of upregulation and the 10 circRNAs with the greatest degree of downregulation were identified. The GO enrichment analysis results indicated that differential circRNA expression may mediate the cellular response to DNA damage, including DNA repair. The KEGG analysis results indicated that the mechanism by which differential circRNA expression exerts these effects may involve the mitogen-activated protein kinases (MAPK) signaling pathway. The GO enrichment analysis of the 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.
The differential expression of circRNAs may play an important role in ARDS, especially in the control of HPMEC permeability. The circRNAs that were shown to have differential expression in response to vascular development and shear stress response could be used as biomarkers for the early prediction of ARDS disease and potential future therapeutic targets.
急性呼吸窘迫综合征（ARDS）的特征是肺微血管通透性升高；然而，环状RNA（circRNA）在此过程中的作用仍不清楚。我们的研究旨在发现circRNA在ARDS肺微血管通透性中发挥作用的潜在机制。
我们使用培养的人肺微血管内皮细胞（HPMECs）和脂多糖刺激建立了ARDS模型。基因组测序揭示了细胞中circRNA表达的显著差异。对靶基因进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。构建了circRNA-微小RNA（miRNA）-信使RNA（mRNA）竞争性内源RNA（ceRNA）网络。对ceRNA网络中靶基因进行了GO富集分析。
基因组测序结果鉴定出379个显著上调的circRNA和448个显著下调的circRNA。确定了上调程度最大的10个circRNA和下调程度最大的10个circRNA。GO富集分析结果表明，circRNA的差异表达可能介导细胞对DNA损伤的反应，包括DNA修复。KEGG分析结果表明，circRNA差异表达发挥这些作用的机制可能涉及丝裂原活化蛋白激酶（MAPK）信号通路。ceRNA网络中靶基因的GO富集分析表明，circRNA主要参与流体剪切应力反应、血管生成调节、血管发育和细胞粘附。
circRNA的差异表达可能在ARDS中起重要作用，尤其是在控制HPMEC通透性方面。在血管发育和剪切应力反应中表现出差异表达的circRNA可作为ARDS疾病早期预测的生物标志物和未来潜在的治疗靶点。
