Department of Immunology and Nano-Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida.
Department of Pharmacology, University of South Alabama, Mobile, Alabama.
Am J Respir Cell Mol Biol. 2019 Dec;61(6):678-688. doi: 10.1165/rcmb.2019-0184TR.
Chronic airway inflammation from recurring exposures to noxious environmental stimuli results in a progressive and irreversible airflow limitation and the lung parenchymal damage that characterizes chronic obstructive pulmonary disease (COPD). The large variability observed in the onset and progression of COPD is primarily driven by complex gene-environment interactions. The transcriptomic and epigenetic memory potential of lung epithelial and innate immune cells drive responses, such as mucus hyperreactivity and airway remodeling, that are tightly regulated by various molecular mechanisms, for which several candidate susceptibility genes have been described. However, the recently described noncoding RNA species, in particular the long noncoding RNAs, may also have an important role in modulating pulmonary responses to chronic inhalation of toxic substances and the development of COPD. This review outlines the features of long noncoding RNAs that have been implicated in regulating the airway inflammatory responses to cigarette smoke exposure and their possible association with COPD pathogenesis. As COPD continues to debilitate the increasingly aging population and contribute to higher morbidity and mortality rates worldwide, the search for better biomarkers and alternative therapeutic options is pivotal.
慢性气道炎症源于反复暴露于有害的环境刺激物，导致进行性和不可逆转的气流受限以及特征性的慢性阻塞性肺疾病（COPD）的肺实质损伤。COPD 的发病和进展中观察到的较大变异性主要由复杂的基因-环境相互作用驱动。肺上皮细胞和固有免疫细胞的转录组和表观遗传记忆潜能驱动反应，如黏液高反应性和气道重塑，这些反应受到多种分子机制的严格调节，已经描述了几个候选易感基因。然而，最近描述的非编码 RNA 种类，特别是长非编码 RNA，也可能在调节对慢性吸入有毒物质的肺部反应和 COPD 的发展方面发挥重要作用。这篇综述概述了长非编码 RNA 的特征，这些特征被认为与调节对香烟烟雾暴露的气道炎症反应有关，并且它们可能与 COPD 的发病机制有关。随着 COPD 继续使日益老龄化的人群衰弱，并导致全球更高的发病率和死亡率，寻找更好的生物标志物和替代治疗选择至关重要。
