Association of MiR-29b/BRD4 with Airway Dysbiosis in Chronic Obstructive Pulmonary Disease after Smoking Cessation

Abstract

Objective

Our earlier research revealed a connection between microRNA-29b (miR-29b) and bromodomain-containing protein 4 (BRD4) and airway inflammation in chronic obstructive pulmonary disease (COPD). We examined their correlation with airway inflammation and dysbiosis in COPD individuals who had ceased smoking.

Methods

Bacterial community composition and diversity were evaluated in bronchoalveolar lavage fluid (BALF) from COPD patients who had ceased smoking, and the expression of miR-29b/BRD4, interleukin (IL)-6 and IL-8 in bronchial brushings was measured. BEAS-2B cells were exposed to COPD BALF filtrate to establish an in vitro model. The expression levels of miR-29b, BRD4, IL-6, and IL-8 were subsequently assessed in these treated cells.

Results

The bacterial community composition in the lungs of individuals with COPD was different from that in the lungs of non-COPD subjects. In COPD patients, lung microbial diversity was significantly reduced, and this decline was correlated with both pulmonary function and airway inflammation. Additionally, the expression of miR-29b was lowered, whereas BRD4 expression was elevated in the lower airways of individuals with COPD. Both miR-29b and BRD4 were linked with pulmonary function, airway inflammation, and diversity indices. miR-29b regulated the production of inflammatory cytokines induced by BALF filtrate through its targeting of BRD4 in bronchial epithelial cells.

Conclusion

Our findings indicate that airway inflammation is associated with airway dysbiosis in COPD patients after smoking cessation and that miR-29b/BRD4 are involved in dysbiosis-associated airway inflammation.

Keywords

Bromodomain-containing protein 4 / Chronic obstructive pulmonary disease / Dysbiosis / Inflammation / MicroRNA

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The Author(s), under exclusive licence to the Huazhong University of Science and Technology