Tweaking lung inflammation in COPD: the "mirky" ways of miRNAs.
Tweaking lung inflammation in COPD: the "mirky" ways of miRNAs.
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调整 COPD 中的肺部炎症：miRNA 的“神秘”方式。
DOI：
10.1152/ajplung.00435.2021
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Polverino,Francesca
中科院分区：
文献类型：
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作者：
Rojas-Quintero,Joselyn;Polverino,Francesca
生物体的复杂性，特别是在慢性阻塞性肺疾病（COPD）等多因素疾病的背景下，不是由基因数量而是由基因调控驱动的。MicroRNA （miRNA）已成为最复杂和最复杂的基因表达调控因子之一，不仅通过诱导直接信使RNA （mRNA）降解和翻译抑制，还通过参与甲基化开关和处理关键转录因子(1)。miRNA是小链RNA， 20-25个核苷酸，通常编码于宿主基因的内含子和外显子中。一些miRNA家族编码为簇(2)。在正常组织发育和疾病中，miRNA参与了大量的过程和反应。在过去的几年中，已经确定了几种mirna是香烟烟雾（CS）诱导的COPD的罪魁祸首。Roffel等人(3)对miR-223-3p在COPD中的表达和功能进行了细致的评估。为了描述miR-223-3p在人类中的表达模式，他们使用了COPD患者和对照组的两个独立筛选和验证队列，呈现了miR-223-3p表达的无偏谱。为了确认miR-223-3p表达模式并进行进一步的相关性分析，使用了来自GLUCOLD（格罗宁根和莱顿大学阻塞性肺疾病皮质类固醇）研究的第三个单独的COPD组。研究发现，与对照组相比，COPD患者肺组织中miR-223-3p的表达增加，并且在大气道样本中，较高的肺miR-223-3p水平与肺功能降低和中性粒细胞炎症增加有关。为了进一步描述miR-223-3p在COPD发展中的作用，作者将野生型（WT）小鼠急性和亚急性暴露于CS，报告在CS暴露后，miR-223-3p在肺组织和支气管肺泡灌胃（BAL）中的表达均增加。急性CS暴露后，在CS暴露的mir -223缺陷小鼠的肺部发现中性粒细胞和单核细胞数量增加。有趣的是，CS暴露4周后，这些对中性粒细胞的影响减弱，而树突状细胞、巨噬细胞和CD8 T细胞的数量增加。作者认为，miR-223可能是急性CS暴露时先天炎症的负调节因子，亚慢性CS暴露可能导致miR-223缺陷小鼠的骨髓和造血功能衰竭。然而，这种对CS的双相反应的机制尚不清楚。鉴于观察到的
The complexity of a living organism, especially in the context of a multifactorial disease such as chronic obstructive pulmonary disease (COPD), is not driven by gene number but gene regulation. MicroRNA (miRNA) has risen to be one of the most intricate and complex gene expression regulators, not only by inducing direct messenger RNA (mRNA) degradation and translation inhibition but also by participating in methylation switches and tackling key transcription factors (1). miRNAs are small strings of RNA, 20–25 nucleotides, usually encoded in introns and exons of host genes, with some miRNA families encoded as clusters (2). miRNAs have been involved in a plethora of processes and responses, both in normal tissue development and in disease. In the last few years, several miRNAs have been identified as culprits in cigarette smoke (CS)-induced COPD. Roffel et al.(3) performed an elegant evaluation of the expression and function of miR-223-3p in COPD. To describe the pattern of miR-223-3p expression in humans, they used two independent screening and validation cohorts of patients with COPD and controls, rendering an unbiased profile of miR-223-3p expression. To confirm miR-223-3p expression pattern and run further correlation analyses, a third separate COPD group from the GLUCOLD (Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease) study was used. The expression of miR-223-3p was found to be increased in lung tissue from patients with COPD when compared with controls, and higher pulmonary levels of miR-223-3p were associated with lower lung function and increased neutrophilic inflammation in large airway samples.To further describe the role of miR-223-3p in COPD development, the authors exposed wild-type (WT) mice acutely and subacutely to CS, reporting miR-223-3pincreased expression in both lung tissue and bronchoalveolar lavage (BAL) upon CS exposure. An increased number of neutrophils and monocytes was found in the lungs from CS-exposed miR-223-deficient mice after acute CS exposure. Interestingly, these effects on neutrophils waned after 4 wk of CS exposure, whereas the numbers of dendritic cells, macrophages, and CD8 T cells increased. The authors suggest that miR-223 might be a negative regulator of innate inflammation upon acute CS exposure and that subchronic CS exposure might lead to exhausted myelopoiesis and hematopoiesis in miR-223-deficient mice. However, the mechanisms underlying this biphasic response to CS are yet to be clarified. Given the observed