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脓毒症诱导的急性肺损伤肺组织中外泌体中非编码RNA和mRNA表达谱的综合分析

Integrated Analysis of Non-Coding RNA and mRNA Expression Profiles in Exosomes from Lung Tissue with Sepsis-Induced Acute Lung Injury.

作者信息

Deng Wei, Lu Yanhua, Hu Ping, Zhang Qingqing, Li Shuangyan, Yang Dong, Zhao Ning, Qian Kejian, Liu Fen

机构信息

Department of Critical Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.

Medical Innovation Center, First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.

出版信息

J Inflamm Res. 2023 Sep 1;16:3879-3895. doi: 10.2147/JIR.S419491. eCollection 2023.

Abstract

BACKGROUND

Acute lung injury (ALI) is associated with a high mortality rate; however, the underlying molecular mechanisms are poorly understood. The purpose of this study was to investigate the expression profile and related networks of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in lung tissue exosomes obtained from sepsis-induced ALI.

METHODS

A mouse model of sepsis was established using the cecal ligation and puncture method. RNA sequencing was performed using lung tissue exosomes obtained from mice in the sham and CLP groups. Hematoxylin-eosin staining, Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and nanoparticle tracking analysis were performed to identify relevant phenotypes, and bioinformatic algorithms were used to evaluate competitive endogenous RNA (ceRNA) networks.

RESULTS

Thirty lncRNA-miRNA-mRNA interactions were identified, including two upregulated lncRNAs, 30 upregulated miRNAs, and two downregulated miRNAs. Based on the expression levels of differentially expressed mRNAs(DEmRNAs), differentially expressed LncRNAs(DELncRNAs), and differentially expressed miRNAs(DEmiRNAs), 30 ceRNA networks were constructed.

CONCLUSION

Our study revealed, for the first time, the expression profiles of lncRNA, miRNA, and mRNA in exosomes isolated from the lungs of mice with sepsis-induced ALI, and the exosome co-expression network and ceRNA network related to ALI in sepsis.

摘要

背景

急性肺损伤(ALI)的死亡率很高;然而,其潜在的分子机制尚不清楚。本研究的目的是调查从脓毒症诱导的ALI小鼠肺组织外泌体中长链非编码RNA(lncRNA)、微小RNA(miRNA)和信使RNA(mRNA)的表达谱及相关网络。

方法

采用盲肠结扎和穿刺法建立脓毒症小鼠模型。对假手术组和CLP组小鼠的肺组织外泌体进行RNA测序。进行苏木精-伊红染色、蛋白质免疫印迹、免疫荧光、定量实时聚合酶链反应和纳米颗粒跟踪分析以鉴定相关表型,并使用生物信息学算法评估竞争性内源RNA(ceRNA)网络。

结果

鉴定出30种lncRNA-miRNA-mRNA相互作用,包括2种上调的lncRNA、30种上调的miRNA和2种下调的miRNA。基于差异表达mRNA(DEmRNA)、差异表达LncRNA(DELncRNA)和差异表达miRNA(DEmiRNA)的表达水平,构建了30个ceRNA网络。

结论

我们的研究首次揭示了脓毒症诱导的ALI小鼠肺组织分离的外泌体中lncRNA、miRNA和mRNA的表达谱,以及脓毒症中与ALI相关的外泌体共表达网络和ceRNA网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/10478974/93cd9ba2d3cc/JIR-16-3879-g0001.jpg

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