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补肾益气方治疗慢性哮喘小鼠的RNA-Seq表达分析及抗气道重塑调控基因靶点预测

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.

作者信息

Cui Jie, Lv Zexi, Teng Fangzhou, Yi La, Tang Weifeng, Wang WenQian, Tulake Wuniqiemu, Qin Jingjing, Zhu Xueyi, Wei Ying, Dong Jingcheng

机构信息

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Institute of Integrative Traditional Chinese and Western Medicine, Fudan University, Shanghai, China.

出版信息

Evid Based Complement Alternat Med. 2021 Jan 18;2021:3524571. doi: 10.1155/2021/3524571. eCollection 2021.

Abstract

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.

摘要

气道重塑是哮喘的典型病理特征之一,而哮喘患者气道的结构变化较为复杂,这阻碍了新型哮喘靶向治疗的发展。我们之前的研究表明,补肺益肾益气方(BSYQF)可通过调节肺部气道炎症和氧化应激来改善慢性哮喘小鼠的气道重塑。在本研究中,我们分析了对照组小鼠以及接受/未接受BSYQF治疗的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%)表达异常的转录本经BSYQF治疗后恢复到完全或部分正常水平。此外,基于之前的结果,我们鉴定出21个差异表达基因(DEG),其倍数变化(FC)>(±)2.0,与炎症、氧化应激、线粒体、PI3K/AKT和MAPK信号通路相关,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脂联素(Adipoq)、分泌性磷蛋白1(SPP1)和腱糖蛋白C(TNC)可能是BSYQF抗重塑作用的关键调节因子。此外,所选4个DEG的定量实时聚合酶链反应(qRT-PCR)结果与RNA-seq分析结果相符。我们的研究结果为BSYQF在哮喘中抗重塑作用的分子机制提供了初步线索。

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