LncTUG1 Regulates miR-181a/BPIFB4 Axis to Promote COPD Inflammation

Chronic obstructive pulmonary disease (COPD) is associated with high mortality and morbidity, with a complex inflammatory mechanism. Previous studies have demonstrated that Bactericidal/Perme Ability-Increasing Fold-Containing Family B member 4 (BPIFB4) plays a significant role in maintaining inflammatory balance. This study aimed to explore the roles of BPIFB4, microRNA (miR)-181a, and long non-coding (lnc) RNA TUG1 in COPD inflammatory processes.

Induced sputum was collected from 20 COPD patients and 20 healthy controls. THP-1 cells were treated with cigarette smoke extract (CSE) to simulate an in vitro inflammatory response. Expression levels of BPIFB4, LncTUG1, and miR-181a were detected by qPCR and western blot. Bioinformatic prediction and dual luciferase assays were used to predict the targeting relationship. Flow cytometry and ELISA assays evaluated the content of macrophages and inflammatory cytokines, respectively.

The expression levels of BPIFB4 and LncTUG1 were elevated in COPD patients, while miR-181a expression was downregulated. BPIFB4 and LncTUG1 were direct targets of miR-181a. Overexpression of BPIFB4 led to increased M2 macrophages and related anti-inflammatory cytokines. In contrast, silencing BPIFB4 resulted in elevated M1 macrophages and associated cytokines. Silencing LncTUG1 elevated miR-181a expression, reduced BPIFB4 expression, and increased M1-type macrophages and pro-inflammatory factors, while overexpression of LncTUG1 showed the opposite effects.

This study concludes that downregulation of LncTUG1 promotes inflammation by reducing BPIFB4 expression through miR-181a. Overexpression of BPIFB4 promotes macrophage polarization toward the M2 type, thereby alleviating the inflammatory response in COPD. These findings provide theoretical support and potential new targets for COPD treatment.