Department of Physiological Sciences, University of Florida , Gainesville, Florida.
Department of Pathology, University of Iowa , Iowa City, Iowa.
Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L133-L148. doi: 10.1152/ajplung.00557.2017. Epub 2018 Apr 5.
Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity (AHR). As a comparison, we also used previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating AHR; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.
主要的治疗方法对一些哮喘患者无效,这表明需要额外的药物。在本研究中,我们使用迷走神经节转录组谱分析和连接映射来确定有益于缓解气道高反应性 (AHR) 的化合物。作为比较,我们还使用了以前发表的致敏小鼠肺和人哮喘支气管活检的转录组数据。所有转录组都揭示了有益于减轻 AHR 的药物;然而,只有迷走神经节转录组鉴定出了临床上用于治疗哮喘的药物(氟尼缩松、异他林)。我们还测试了一种通过迷走神经节转录组谱分析鉴定出的以前与哮喘无关的化合物,发现它对小鼠和猪的气道均有支气管扩张作用。这些数据表明,迷走神经节转录组谱分析可能是一种识别潜在哮喘治疗药物的新策略。