Li Xia1, Xiang Wang1, Lijuan Liu2, Jinrong Fu2, Wenfeng Xiao1, Qiuyan Liang1, Xiao Han1, Saihua Huang1, Licheng Sun1, Yajing Gao1, Caiyan Zhang1, Lan Yang1, Libo Wang3, Liling Qian4, Yufeng Zhou5. 1. 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. 2. 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; Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China. 3. Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China. 4. Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China. Electronic address: llqian@126.com. 5. 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; National Health Commission Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China. Electronic address: yfzhou1@fudan.edu.cn.
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.
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.