Francisco-Garcia Ana S, Garrido-Martín Eva M, Rupani Hitasha, Lau Laurie C K, Martinez-Nunez Rocio T, Howarth Peter H, Sanchez-Elsner Tilman
Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
NIHR Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research MP812, Southampton General Hospital, Southampton SO16 6YD, UK.
Noncoding RNA. 2019 Nov 2;5(4):51. doi: 10.3390/ncrna5040051.
MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.
已知微小RNA可调节哮喘病理过程中的重要信号通路，包括白细胞介素-6和干扰素信号通路。微小RNA不仅存在于细胞内，也存在于细胞外囊泡（如外泌体）中。在本研究中，我们特别关注重症哮喘患者支气管肺泡灌洗中纳米囊泡携带的微小RNA。我们采用连续过滤法提取纳米囊泡RNA。使用小RNA测序分析RNA含量，并通过WebGestalt 2017软件将其映射到受影响的信号通路。我们报告称，重症哮喘患者气道腔纳米囊泡中微小RNA的装载不足，且小RNA纳米囊泡含量（即核糖体RNA和断裂转录本等）的图谱发生改变。预计这种微小RNA携带量的减少会通过促进炎症和重塑来增加基因表达。同样，在重症哮喘中，一个微小RNA网络与第一秒用力呼气容积降低以及嗜酸性粒细胞和中性粒细胞炎症增加相关。因此，气道纳米囊泡中的微小RNA可能是定义重症哮喘异常生物学疾病过程和监测介入治疗效果的有效生物标志物。
