Circular RNA expression in the lungs of a mouse model of sepsis induced by cecal ligation and puncture

Yuan, Caiyun; Gu, Jie; Wu, Jing; Yin, Jiangwen; Zhang, Mengjie; Miao, Hongjun; Li, Jun

doi:10.1016/j.heliyon.2020.e04532

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…Some miRNAs have been reported to regulate inflammation; for example, miRNA-208-5p regulates myocardial injury in septic mice [ 44 ], and miRNA-29 promotes pancreatic β cell inflammation via TRAF3 [ 45 ]. CircRNAs or lncRNAs, which act as miRNAs, were significantly differentially expressed in the ALI group in this study and the previous study of ALI [ 46 , 47 ]. It has also been recognized that circANKR inhibits the NF-κB signaling pathway by acting on the miR-31/MyD88 axis [ 48 ], and lncRNA TUG1 also alleviates sepsis-induced acute lung injury by targeting miRNA-34b-5p [ 49 ].…”

Section: Discussionsupporting

confidence: 76%

Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

Zhang

Nie

et al. 2022

BMC Genomics

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Sympathetic nerves play essential roles in the regulation of lung inflammation, and we investigated the effect of sympathetic denervation (SD) on sepsis-induced acute lung injury (ALI) in mice. Mice were randomized to the control, SD, ALI and SD + ALI, groups. SD and ALI were established through intratracheal 6-hydroxydopamine and intraperitoneal lipopolysaccharide, respectively. Models and gene expressions levels were evaluated by HE staining, ELISA, Western blotting and RT-qPCR. RNA extraction, whole transcriptome sequencing and subsequent biostatistical analysis were performed. Sympathetic denervation in the lungs significantly attenuated lung TNF-ɑ and norepinephrine expression, alleviated sepsis-induced acute lung injury and inhibited NF-κB signaling. Compared with the ALI group, the SD + ALI group exhibited 629 DE circRNAs, 269 DE lncRNAs,7 DE miRNAs and 186 DE mRNAs, respectively. Some DE RNAs were validated by RT-qPCR. CircRNA–miRNA–mRNA regulatory networks in the SD + ALI group revealed enrichment of the B-cell receptor signaling pathway, IL-17 signaling pathway, neuroactive ligand–receptor interaction, CAM, primary immunodeficiency, and cytokine–cytokine receptor interaction terms. The lncRNA-miRNA-mRNA network also revealed inflammation–related signaling pathways. Taken together, based on the successfully established models of SD and ALI, we show here that sympathetic nerves may regulate sepsis-induced ALI supposedly by affecting the expression of circRNAs, lncRNAs, miRNAs, and mRNAs in the lungs. These results may allow for further exploration of the roles of pulmonary sympathetic nerves in sepsis-induced ALI.

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Section: Discussionsupporting

confidence: 76%

Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

Zhang

Nie

et al. 2022

BMC Genomics

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“…Acute respiratory distress syndrome (ARDS) or ALI is a devastating disease characterized by dysregulated immune responses, endothelial activation, and microvascular thrombosis [ 11 ]. Recently, several circRNAs have been identified to regulate the inflammatory response and cell apoptosis of pulmonary ECs through downstream miRNAs [ 12 ]. In the present study, we performed transcriptomic profiling to evaluate the expression of circRNAs in sepsis patients.…”

Section: Discussionmentioning

confidence: 99%

The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis

Shen

Yan

Zhang

et al. 2022

Aging

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Sepsis-induced acute lung injury (ALI) is a severe cause of death. Increasing evidence has identified circular RNAs (circRNAs) acting as critical regulators of human diseases. However, their expression pattern and underlying mechanisms in ALI remain unclear. Herein, we screened the circRNAs of ALI patients and constructed a lung injury murine model using lipopolysaccharides (LPS) induction. Functional analyses of targeted circRNA were performed in vivo and in vitro . Then, the downstream miRNA and mRNA of specific circRNAs were identified. Compared to healthy subjects, 35 circRNAs were upregulated and 9 circRNAs were downregulated in sepsis patients. The top 10 differentially expressed circRNAs were selected for validation and has_circ_0003091 was selected. The ALI mice presented significantly elevated has_circ_0003091 (mmu_circ_0015268). The functional analysis revealed that mmu_circ_0015268 contributed to the pulmonary injury, cell apoptosis, inflammatory responses, and endothelial activation in the ALI murine model. On the other hand, silencing mmu_circ_0015268 showed protective effects in LPS-treated mice and PMVECs. Furthermore, mmu_circ_0015268 sponged miR-149 to upregulate the expression of its target Smad2. In summary, we demonstrated that has_circ_0003091 might be a novel target for the management and treatment of sepsis-induced ALI.

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“…Circular RNAs (circRNAs) are a family of noncoding RNAs presenting crucial roles in regulating normal physiology and pathological developments. Several studies using systemic approaches and/or bioinformatics analysis all evidenced an altered expression profile of circRNAs in ALI (Bao et al, 2019;Li et al, 2019;Yuan et al, 2020;Jiang et al, 2020b), supporting their importance in ALI development. In contrast, the mechanistic understanding of specific circRNAs in ALI is still in its infancy (Zou et al, 2020;Yang et al, 2021) and largely remains to be revealed. To expand our understanding of circRNAs in ALI, we followed up on circEXOC5 (hsa_circ_0004399), one of the most significantly up-regulated circRNAs identified by microarray and verified by qRT-PCR in lung macrophages from CLP mice as compared to those from sham-operated mice (Bao et al, 2019).…”

Section: Introductionmentioning

confidence: 90%

circEXOC5 promotes acute lung injury through the PTBP1/Skp2/Runx2 axis to activate autophagy

Gao

Ding

et al. 2022

Life Sci. Alliance

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To understand the pathogenesis of acute lung injury (ALI), we focused on circEXOC5, a significantly up-regulated circular RNA in ALI. Using the in vivo cecal ligation and puncture (CLP)–induced ALI mouse model and in vitro LPS-challenged mouse pulmonary microvascular endothelial cell (MPVEC) model, we examined the impacts of knockdown circEXOC5 on lung injury, inflammation, and autophagy. The regulation between circEXOC5, polypyrimidine tract-binding protein 1 (PTBP1), S-phase kinase-associated protein 2 (Skp2), and Runt-related transcription factor 2 (Runx2) was investigated by combining RNA immunoprecipitation, qRT–PCR, mRNA stability, and ubiquitination assays. The significance of PTBP1 in circEXOC5-induced ALI phenotypes was examined both in vitro and in vivo. circEXOC5 was up-regulated and associated with increased inflammation and activated autophagy in cecal ligation and puncture–induced ALI lung tissues and LPS-challenged MPVECs. Through the interaction with PTBP1, circEXOC5 acceleratedSkp2mRNA decay, an E3 ubiquitin ligase for Runx2, and therefore increased Runx2 expression. Functionally, overexpressing PTBP1 reversed shcircEXOC5-inhibited ALI, inflammation, or autophagy. The signaling cascade circEXOC5/PTBP1/Skp2/Runx2, by essentially regulating inflammation and autophagy in MPVECs, aggravates sepsis-induced ALI.

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Circular RNA expression in the lungs of a mouse model of sepsis induced by cecal ligation and puncture

Cited by 11 publications

References 23 publications

Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis

circEXOC5 promotes acute lung injury through the PTBP1/Skp2/Runx2 axis to activate autophagy

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