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.