Inhibition of miR-34a reduces inflammatory response in acute exacerbation of chronic obstructive pulmonary disease

Abstract

Objective To observe the expression levels and related mechanisms of miR-34a and its inflammatory-related factors in broncho-alveolar lavage fluid of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Totally 20 patients with acute exacerbation of COPD were recruited as the study group and 20 patients in stable period of COPD were recruited as control group. Bronchoalveolar lavage fluid was collected, A549 cell was cultured and AECOPD cell model was built for evaluating the effects of over-expression of miR-34a, inhibition of miR-34a, and silencing of HIF-1α in cells. ELISA assay was applied to detect the expression of inflammatory factors IL-6, IL-8, TNF-αand TGF-β in bronchoalveolar lavage fluid and cell supernatant. The expression of miR-34a and HIF-1 αwere measured by RT-qPCR, and Western blot was used to detect the expression of HIF-1α. Results Compared with the control group, the expression of inflammatory factors, miR-34a, and HIF-1α in the AECOPD group were significantly elevated (P＜0.05). Over-expression of miR-34a led to further elevation of HIF-1α and inflammatory factor expression (P＜0.05). Inhibition of miR-34a resulted in a significant decrease of HIF-1α and inflammatory factors (P＜0.05). The expression of HIF-1α in the AECOPD group was significantly elevated (P＜0.05), and silencing HIF-1α significantly reduced the expression of inflammatory factors(P＜0.05). The expression of miR-34a had no significant change. Conclusions miR-34a is involved in the inflammatory damage in patients with acute exacerbation of COPD by regulating HIF-1α. Interfering with the miR-34a/HIF-1α pathway alleviates inflammatory response, so it is a potential target in the treatment of acute exacerbation of COPD.

Keywords

• acute exacerbation of chronic obstructive pulmonary disease (aecopd)|inflammatory response|mir-34a|hypoxia inducible factor-1α (hif-1α)