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过敏性哮喘儿童的特定微小RNA谱及功能网络

The Specific microRNA Profile and Functional Networks for Children with Allergic Asthma.

作者信息

Zhang Xiyan, Zhang Xude, Feng Shaojie, Wang Xijuan, Guo Beibei, Liu Jingjing, Xu Donghua, Liu Fengxia

机构信息

Department of Allergy, Weifang People's Hospital, Weifang, People's Republic of China.

Clinical Medicine College, Weifang Medical University, Weifang, People's Republic of China.

出版信息

J Asthma Allergy. 2022 Aug 29;15:1179-1194. doi: 10.2147/JAA.S378547. eCollection 2022.

DOI:10.2147/JAA.S378547
PMID:36059920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9439701/
Abstract

BACKGROUND

Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study.

OBJECTIVE

This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma.

MATERIALS AND METHODS

In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs.

RESULTS

One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma.

CONCLUSION

We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.

摘要

背景

过敏性哮喘是最常见的哮喘类型,常于早年发病,且合并症不断增加,包括特应性皮炎和过敏性鼻炎。微小RNA(miRNA)参与多种免疫和炎症性疾病的发病机制,尤其是过敏性炎症。过敏性哮喘患儿的特定miRNA谱尚未完全明确,仍需深入研究。

目的

本研究旨在鉴定miRNA的表达谱,并构建差异表达的miRNA与靶mRNA之间的相互作用网络,为理解过敏性哮喘的发病机制提供新见解。

材料与方法

在本研究中,我们对哮喘急性期儿童的外周血单个核细胞(PBMC)进行了高通量测序。采用包括miRanda、基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库在内的生物信息学方法,预测过敏性哮喘的新治疗和诊断靶点。进行实时定量PCR以检测异常表达的miRNA的表达。

结果

在过敏性哮喘患儿中鉴定出161个差异表达的miRNA,包括140个保守miRNA和21个新miRNA。预测了总共8929个与差异表达的miRNA相关的靶mRNA(44,186个转录本),并在cGMP-PKG信号通路、胆碱能突触和唾液分泌中显著富集。我们还发现miRNA-370-3p靶向cGMP-PKG信号通路中的PKG和MLCP分子,并参与过敏性哮喘的发病机制。

结论

我们鉴定了过敏性哮喘患儿PBMC的miRNA谱,还发现miRNA-370-3p靶向cGMP-PKG信号通路中的PKG和MLCP分子,这为理解过敏性哮喘的发病机制和研究儿童过敏性哮喘的新治疗靶点提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3061/9439701/a1d61012bb52/JAA-15-1179-g0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3061/9439701/a42910d8cde3/JAA-15-1179-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3061/9439701/a1d61012bb52/JAA-15-1179-g0009.jpg

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