Whole transcriptome analysis of the differential RNA profiles and associated competing endogenous RNA networks in LPS-induced acute lung injury (ALI)

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251359
Xiangnan Teng ◽  
Jing Liao ◽  
Lili Zhao ◽  
Wei Dong ◽  
Haiyi Xue ◽  

Acute lung injury (ALI) is a serious inflammation disease usually arises alveolar epithelial membrane dysfunction and even causes death. Therefore, the aims of this study are to screen the differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs in ALI based on the high-throughput sequencing. The lipopolysaccharide (LPS)-induced ALI mouse model was established, the injury of ALI mouse model was evaluated through histological analysis with hemotoxylin and eosin (H & E) staining assay, dry/wet ratio, infiltrated-immune cells, ET-1 mRNA expression and released-proinflammation factors. Then, expression data of lncRNAs, circRNAs, miRNAs and mRNAs in ALI were acquired using whole-transcriptome sequencing. The differential expression of lncRNAs (DE lncRNAs), circRNAs (DE circRNAs), miRNAs (DE miRNAs) and mRNAs (DE mRNAs) were identified, and the lncRNA-miRNA-mRNA network and circRNA-miRNA-mRNA network were constructed, and the biological function of target genes were annotated based on bioinformatics analysis. In the present study, the LPS-induced ALI mouse model was successfully established. The biological analysis results showed that total 201 DE lncRNAs, 172 DE circRNAs, 62 DE miRNAs, and 3081 DE mRNAs were identified in ALI. The 182 lncRNA-miRNA-mRNA networks and 32 circRNA-miRNA-mRNA networks were constructed were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The biological function analysis indicated that TNF signaling pathway, chemokine signaling pathway and so on involved in ALI. In the present study, the differential expression coding and non-coding RNAs (ncRNAs) in ALI were identified, and their regulatory networks were constructed. There might provide the potential biomarkers and underlying mechanism for ALI diagnosis and treatment.

2018 ◽  
Vol 40 (6) ◽  
pp. 769-780 ◽  
Jian Lou ◽  
Yue Hu ◽  
Min-dan Wu ◽  
Luan-qing Che ◽  
Yin-fang Wu ◽  

2015 ◽  
Vol 4 (6) ◽  
pp. 1587-1596 ◽  
Suhua Wang ◽  
Yanrong Gao ◽  
Lihua Huang ◽  
Shanshan Zheng ◽  
Chunxia Wang ◽  

The activation mechanism of the NF-κB signaling pathway in Nd2O3exposure-induced acute lung inflammation and pneumoconiosis.

2021 ◽  
Vol 41 (1) ◽  
Wuquan Li ◽  
Wentao Zhang ◽  
Jun Liu ◽  
Yalong Han ◽  
He Jiang ◽  

Abstract Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.

2019 ◽  
Vol 39 (5) ◽  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

2018 ◽  
Vol 234 (4) ◽  
pp. 4641-4654 ◽  
Wen-Jing Zhong ◽  
Hui-Hui Yang ◽  
Xin-Xin Guan ◽  
Jian-Bing Xiong ◽  
Chen-Chen Sun ◽  

2018 ◽  
Vol 233 (9) ◽  
pp. 6615-6631 ◽  
Wang Xie ◽  
Qingchun Lu ◽  
Kailing Wang ◽  
Jingjing Lu ◽  
Xia Gu ◽  

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Lisa E. Gralinski ◽  
Armand Bankhead ◽  
Sophia Jeng ◽  
Vineet D. Menachery ◽  
Sean Proll ◽  

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI.

Transfusion ◽  
2013 ◽  
Vol 54 (4) ◽  
pp. 996-1001 ◽  
Marcella C.A. Müller ◽  
Pieter R. Tuinman ◽  
Koenraad F. van der Sluijs ◽  
Louis Boon ◽  
Joris J. Roelofs ◽  

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