The role of lncRNA in the pathogenesis of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible airflow obstruction with abnormal lung function. Because its pathogenesis involves multiple aspects of oxidative stress, immunity and inflammation, apoptosis, airway and lung repair and destruction, the clinical approach to COPD treatment is not further updated. Therefore, it is crucial to discover a new means of COPD diagnosis and treatment. COPD etiology is associated with complex interactions between environmental and genetic determinants. Numerous genes are involved in the pathogenic process of this illness in research samples exposed to hazardous environmental conditions. Among them, Long non-coding RNAs (lncRNAs) have been reported to be involved in the molecular mechanisms of COPD development induced by different environmental exposures and genetic susceptibility encounters, and some potential lncRNA biomarkers have been identified as early diagnostic, disease course determination, and therapeutic targets for COPD. In this review, we summarize the expression profiles of the reported lncRNAs that have been reported in COPD studies related to environmental risk factors such as smoking and air pollution exposure and provided an overview of the roles of those lncRNAs in the pathogenesis of the disease.

Keywords: Air pollution; Chronic Obstructive Pulmonary Disease (COPD); Cigarette smoke; Environmental exposure; Long non-coding RNAs (lncRNAs).

Fig. 1

Diagrammatic representation of COPD etiology and pathogenesis. Risk factors for COPD include smoking and air pollution, and so on. When irritants and toxicants are inhaled, the structural cells of the lung, such as epithelial cells, fibroblasts, and endothelial cells, get activated. When bronchial epithelial cells are damaged, alarm molecules (TSLP, IL-33, IL-25) are released, activating a variety of immune cells, endothelial cells, and fibroblasts. These cells release inflammatory mediators, which attract other inflammatory cells such as neutrophils, macrophages, and lymphocytes to the exposed area, resulting in persistent airway inflammation.

Fig. 2

Heat maps displaying the differential expression and hierarchical clustering of lncRNAs in (A) smokers with no COPD (SNC) compared with non-smokers without COPD (NS) and in (B) COPD patients compared with SNC. Reprinted with permission from Ref. [39]. Copyright (2015) Springer Link.

Fig. 3

Heat maps displaying the differential expression and hierarchical clustering of lncRNAs in (A) WSPM2.5 and (B) TAPM2.5 concentrations stimulation. Reprinted with permission from Ref. [44]. Copyright (2018) Portland Press.

Fig. 4

Triggers of COPD exacerbations and associated pathophysiological changes leading to increased exacerbation symptoms.

Fig. 5

MicroRNAs may be captured by lncRNAs like a sponge. By attaching to these microRNAs, they stop microRNAs from attaching to their target mRNAs, eliminating post-transcriptional control.