Characteristics of circular RNA expression of pulmonary macrophages in mice with sepsis‐induced acute lung injury

Abstract

Circular RNAs (circRNAs) make up a large class of non‐coding RNAs and play important roles in the pathology of a variety of diseases. However, their roles in pulmonary macrophage polarization after sepsisinduced lung injury is unknown. In this study, mice were divided into two groups: Sham control group and cecal ligation and puncture (CLP)‐induced ALI group. Macrophages were isolated from lung homogenates 24 hours after SCLP/CLP. We started with RNA‐seq of circRNA changes in macrophages and validated by RT‐PCR in the following experiments. A total of 4318 circRNAs were detected in the two groups. Of these, 11 and 126 circRNAs were found to be significantly upregulated and downregulated, respectively, compared to the control (p≤0.05, Fold Change ≥2). Differentially expressed circRNAs with a high foldchange (fold‐change >4, P<0.05) were selected for validation by qRT‐PCR, 10 of which were verified. Furthermore, the most differentially expressed circRNAs within all the comparisons were annotated in detail with circRNA/miRNA interaction information using miRNA target prediction software. The network of circRNA‐miRNA‐mRNA was illustrated by cytoscape software. Gene ontology analyses indicated the upregulated circRNAs were involved in the multiple biological functions such as regulation of mitochondrion distribution and Notch binding, while the down‐regulated circRNAs mainly involved in the biological process as histone H3K27 methylation. KEGG pathway analysis revealed TGF‐beta signaling pathway was related to the upregulated circRNAs. The present study provides a novel insight into the roles of circRNAs in pulmonary macrophage differentiation and polarization post septic lung injury.

MNK as a potential pharmacological target for suppressing LPS-induced acute lung injury in mice

“…Lipopolysaccharide (LPS), a main component of bacterial cell walls, has been identified as a key factor in ALI development, which can trigger a rapid and robust inflammatory response and impair the normal function of immune cells, such as macrophages. Results from previous studies showed that continuous activation of macrophages was one of the key steps responsible for accelerating ALI progress [9] , [10] , [11] , [12] . Macrophages perform multiple functions at different stages of ALI through the production of pro-inflammatory mediators including chemokines and cytokines such as interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) [13] , [14] , [15] .…”

Protective effects of P2X7R antagonist in sepsis‐induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression

“…reported that circRNA HECTD1 promoted silica‐induced pulmonary endothelial–mesenchymal transition via the gene HECTD1 . Additionally, the circRNAs chr17:71273374–71275287‐, chr14:57733878–57734418‐ and chr18:10119885–10132272‐ were reported to be up‐regulated in injured lung tissue after sepsis‐induced ALI, indicating the role of circRNAs in pulmonary macrophage differentiation and polarization 22 . In the present study, we found and confirmed that mmu_circ_0001679 and mmu_circ_0001212 expression was significantly up‐regulated in the lung tissues of sepsis + DMSO mice compared to that in sham mice and significantly decreased after treatment with the P2X 7 R antagonist A‐438079.…”

“…Li et al 21 observed significantly changed circRNA profiles and revealed a potential role of circRNAs in a mouse model of LPS-induced ALI. Bao et al 22 reported many circRNAs of dysregulated expression in the pulmonary macrophages of mice with sepsis-induced ALI. mRNA transcripts from genomic DNA are crucial in many diseases.…”

Identification and integrated analysis of CircRNA and miRNA of Radiation-Induced lung injury in a mice model

“…In recent years, microRNA and circRNA sequencing techniques were broadly used to recognize potential targets from the complex RNA networks based on the models of varies disease (26)(27)(28). Sequencing of circRNAs were even performed in the RIEI mice model and sepsis-induced acute lung injury (29), these previous studies have successfully provided meaningful potential target or mechanism for the diseases, respectively. To our knowledge, this is the rst study analyzing the relationship of RILI and circRNAs by using RNA-seq data and computational approaches to identify the differentially expressed miRNAs and circRNAs.…”