Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients.

Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients.
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DOI:
10.3390/ijms222111830
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发表时间:
2021-10-31
影响因子:
5.6
通讯作者:
Rahman I
Rahman I
中科院分区:
生物学2区
文献类型:
--
作者:
Kaur G;Maremanda KP;Campos M;Chand HS;Li F;Hirani N;Haseeb MA;Li D;Rahman I

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慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)是慢性进行性肺部疾病,具有不同的病理特征。对于这些衰弱的疾病,缺乏早期检测的生物标志物和发病机制。细胞外小泡(EV),包括外体,是一种小的、与脂质结合的小泡,在正常和疾病条件下,携带蛋白质、脂类和RNA分子以促进细胞间的通讯。已有研究表明外体miRNAs与许多疾病有关。然而,对于COPD和IPF患者的支气管肺泡灌洗液(BALF)或肺组织来源的外切体的miRNA群体知之甚少。在这里,我们测定并比较了独立队列中健康的非吸烟者、吸烟者和COPD或IPF患者的BALF和肺组织来源的外切体的miRNA图谱。结果:纳米颗粒示踪和透射电子显微镜表征表明,BALF来源的外切体的大小为89.85 nm,浓度为2.95×1010个/mL。肺源性外切体的体积较大(~146.04 nm),产率较高,为2.38×1011粒/毫升。NGS结果发现在BALF中有三个差异表达的miRNAs,而与健康的非吸烟者相比,COPD患者的肺来源外体中有一个。其中,与健康的非吸烟者和吸烟者相比,在COPD患者的肺组织来源的外体中,miR-122-5p的表达分别下调了三到五倍。有趣的是,与非吸烟对照组相比,IPF患者肺组织来源的外切体中有大量差异表达的miRNAs(55个)。结论:总体而言,我们确定了与慢性肺部疾病相关的肺特异miRNAs,它们可以作为潜在的生物标记物或治疗靶点。
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets.
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