lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma through stabilizing BAZ2B pre-mRNA - 04/03/21
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
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.]). |
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Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 3
P. 921 - Marzo 2021 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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