Association of MiR-29b/BRD4 with Airway Dysbiosis in Chronic Obstructive Pulmonary Disease after Smoking Cessation
摘要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 correla-tion 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 smok-ing cessation and that miR-29b/BRD4 are involved in dysbiosis-associated airway inflammation.
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