Exosomal miR-129-2-3p promotes airway epithelial barrier disruption in PM2.5-aggravated asthma

Particulate matter 2.5 (PM2.5) exposure is intricately linked to asthma exacerbations. Damage to the airway epithelial barrier function serves as an initiating factor for asthma attacks and worsening symptoms. In recent years, numerous exosomal microRNAs (miRNAs) have emerged as potential biomarkers for diagnosing asthma. However, the mechanisms by which PM2.5- induced exosomes exacerbate asthma remain unclear. This study aims to investigate the role of exosomal miR-129-2-3p in regulating airway epithelial cell barrier function, its potential targets, and signaling pathways involved in PM2.5- induced aggravation of asthma. In this study, miR-129-2-3p is highly expressed in plasma exosomes from patients with asthma, mouse lung tissue and plasma exosomes, and exosomes produced by PM2.5-stimulated 16HBE cells. Moreover, the exposure level of PM2.5 is positively correlated with exosomal miR-129-2-3p in plasma in patients with asthma. As the concentration of PM2.5 increases, the synthesis of connexin (ZO-1, occludin, and E-cadherin) is gradually weakened, while the content of inflammatory factors (IL-6, IL-8, and TNF-alpha) is notably upregulated in PM2.5 exacerbated asthmatic mice. PM(2.5 )induced exosomes can decrease the level of connexin, enhance cell permeability and promote the secretion of inflammatory factors in 16HBE cells. TIAM1, a specific target gene for miR-129-2-3p, regulates the synthesis of connexin. Exosomal miR-129-2-3p exacerbates airway epithelial barrier dysfunction by targeted inhibition of the TIAM1/RAC1/PAK1 signaling pathway in PM2.5 aggravated asthma. In contrast, blocking miR-129-2-3p may be an alternative approach to therapeutic intervention in asthma.