RNA-Seq Expression Analysis of Chronic Asthmatic Mice with Bu-Shen-Yi-Qi Formula Treatment and Prediction of Regulated Gene Targets of Anti-Airway Remodeling.
RNA-Seq Expression Analysis of Chronic Asthmatic Mice with Bu-Shen-Yi-Qi Formula Treatment and Prediction of Regulated Gene Targets of Anti-Airway Remodeling.
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DOI：
10.1155/2021/3524571
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Dong J
中科院分区：
文献类型：
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作者：
Cui J;Lv Z;Teng F;Yi L;Tang W;Wang W;Tulake W;Qin J;Zhu X;Wei Y;Dong J
气道重塑是哮喘的典型病理特征之一，而哮喘气道结构变化复杂，阻碍了哮喘新型靶向治疗的发展。我们之前的研究表明，补肾益气方（BSYQF）可以通过调节气道炎症和肺部氧化应激来改善慢性哮喘小鼠的气道重塑。在本研究中，我们分析了接受/未接受 BSYQF 治疗的对照小鼠和哮喘小鼠模型的肺转录组。通过 RNA 测序 (RNA-seq) 分析，我们发现哮喘小鼠中 264/1746 (15.1%) 表现异常表达的转录物通过 BSYQF 治疗恢复到完全或部分正常水平。此外，基于先前的结果，我们鉴定了21个与炎症、氧化应激、线粒体、PI3K/AKT和MAPK信号通路相关的倍数变化(FC) > (±) 2.0的差异表达基因(DEG)，这些基因可能在BSYQF治疗的抗重塑作用机制中发挥重要作用。通过将21个DEG输入IPA数据库构建基因网络，我们推断位于网络关键节点的Adipoq、SPP1和TNC可能是BSYQF抗重塑作用的关键调节因子。此外，所选四个DEG的定量实时聚合酶链反应（qRT-PCR）结果与RNA-seq分析的结果相匹配。我们的结果为 BSYQF 抗哮喘重塑作用的分子机制提供了初步线索。
Airway remodeling is one of the typical pathological characteristics of asthma, while the structural changes of the airways in asthma are complex, which impedes the development of novel asthma targeted therapy. Our previous study had shown that Bu-Shen-Yi-Qi formula (BSYQF) could ameliorate airway remodeling in chronic asthmatic mice by modulating airway inflammation and oxidative stress in the lung. In this study, we analysed the lung transcriptome of control mice and asthmatic mouse model with/without BSYQF treatment. Using RNA-sequencing (RNA-seq) analysis, we found that 264/1746 (15.1%) of transcripts showing abnormal expression in asthmatic mice were reverted back to completely or partially normal levels by BSYQF treatment. Additionally, based on previous results, we identified 21 differential expression genes (DEGs) with fold changes (FC) > (±) 2.0 related to inflammatory, oxidative stress, mitochondria, PI3K/AKT, and MAPK signal pathways which may play important roles in the mechanism of the anti-remodeling effect of BSYQF treatment. Through inputting 21 DEGs into the IPA database to construct a gene network, we inferred Adipoq, SPP1, and TNC which were located at critical nodes in the network may be key regulators of BSYQF's anti-remodeling effect. In addition, the quantitative real-time polymerase chain reaction (qRT-PCR) result for the selected four DEGs matched those of the RNA-seq analysis. Our results provide a preliminary clue to the molecular mechanism of the anti-remodeling effect of BSYQF in asthma.