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lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma through stabilizing BAZ2B pre-mRNA - 04/03/21

Doi : 10.1016/j.jaci.2020.06.034 
Li Xia, MS a, , Xiang Wang, PhD a, , Lijuan Liu, MD a, b, , Jinrong Fu, MD, PhD a, b, , Wenfeng Xiao, BS a, Qiuyan Liang, BS a, Xiao Han, PhD a, Saihua Huang, MS a, Licheng Sun, PhD a, Yajing Gao, BS a, Caiyan Zhang, MS a, Lan Yang, BS a, Libo Wang, MD b, Liling Qian, MD, PhD b, , Yufeng Zhou, MD, PhD a, c,
a Institute of Pediatrics, Children’s Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China 
b Department of Respiratory Medicine, Children’s Hospital of Fudan University, Shanghai, China 
c National Health Commission Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China 

Corresponding author: Yufeng Zhou, MD, PhD, 399 Wanyuan Rd, Minhang, Shanghai 201102, China.399 Wanyuan RdMinhangShanghai201102China∗∗Liling Qian, MD, PhD, 399 Wanyuan Rd, Minhang, Shanghai 201102, China.399 Wanyuan RdMinhangShanghai201102China

Abstract

Background

Dysregulation of long noncoding RNAs (lncRNAs) is associated with a variety of human diseases; however, whether they have a role in childhood asthma is unknown.

Objective

We sought to determine the differential expression profiles of lncRNAs in PBMCs of children with asthma and the mechanisms underlying the effects of lncRNAs on the pathogenesis of asthma.

Methods

The differential expression profiles of lncRNAs were analyzed by transcriptome microarray. The effects and mechanisms by which lncRNAs influence macrophage activation were detected by real-time quantitative PCR, Western blot, RNase protection assay, and chromatin immunoprecipitation assay. The roles played by lncRNAs in asthma were tested in a cockroach allergen extract (CRE)-induced mouse model.

Results

We identified 719 lncRNAs that were differentially expressed in PBMCs of children with asthma, 502 of which were upregulated and 217 were downregulated. An lncRNA of unknown function, lnc-BAZ2B, was dominantly expressed in monocytes and significantly upregulated in children with asthma. lnc-BAZ2B promotes M2 macrophage activation by enhancing BAZ2B expression and exacerbated lung inflammation in an M2 macrophage–associated CRE-induced asthma model. Mechanistically, lnc-BAZ2B promoted the expression of its cis target gene BAZ2B by stabilizing its pre-mRNA. BAZ2B, a reader of H3K14ac modification, enhanced the transcription of IRF4 and promoted M2 macrophage activation. lnc-BAZ2B expression was correlated with that of BAZ2B in PBMCs from children with asthma. Baz2b knockdown could alleviate asthma severity in a CRE-induced asthma model.

Conclusion

lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma and may serve as a potential therapeutic and diagnostic target in children with asthma.

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Graphical abstract




Il testo completo di questo articolo è disponibile in PDF.

Key words : Asthma, lncRNA, macrophage activation, BAZ2B

Abbreviations used : BAZ2B, ChIP, CRE, FC, IRF4, lncRNA, miRNA, PARγ, RT-qPCR, siRNA


Mappa


 This work was supported by grants from the National Key R&D Program of China (grant 2016YFC1305102 [to Y.Z.]), the National Natural Science Foundation of China (grants 81671561 and 81974248 to [Y.Z.] and grant 81900751 to [H.X.]), the International Joint Laboratory Program of National Children’s Medical Center (grant EK1125180109 to [Y.Z.]), the Program for Outstanding Medical Academic Leader (grant 2019LJ19 [to Y.Z.]), the Shanghai Municipal Planning Commission of Science and Research Fund (grants 201740065 [to Y.Z.] and 20174Y0079 [to H.X.]), the Shanghai Pujiang Program (16PJ1401600 [to F.J.]), and the Shanghai Committee of Science and Technology (grants 19ZR1406400 [to F.J.] and 16411950700 [to L.Q.]).
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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