MiR-186-5p carried by M2 macrophage-derived exosomes downregulates TRPP2 expression in airway smooth muscle to alleviate asthma progression

Bronchial asthma (asthma) is a chronic inflammatory disease of the airways that remains an unresolved problem. Reportedly M2 macrophages and exosomes play a role in inflammation, including asthma. We investigated the roles of M2 macrophage-derived exosomes (M2-Exos) effect in asthmatic progression by using ovalbumin (OVA) induced asthmatic mice model. M2-Exos significantly ameliorated the pulmonary inflammatory response and airway hyperresponsiveness in asthmatic mice and suppressed aberrant proliferation and transient receptor potential polycystic protein 2(TRPP2) expression in LPS-stimulated primary airway smooth muscle cells (ASMCs). Then, we found that miR-186-5p of M2-Exos could target TRPP2 through online database analysis. However, miR-186-5p downregulation by miR-186-5p inhibitors decreased the protective effect of M2-Exos in asthmatic mouse and cellular models. miR-186-5p was identified and selectively combined with the polycystin-2 gene encoding TRPP2 protein, inhibited TRPP2 protein production, and downregulated TRPP2 expression. A reduction in the number of TRPP2 calcium (CA) channels formed on the cell membrane leads to a decreased intracellular CA²⁺ concentration ([CA²⁺] _i), causing reduced ASMC contraction and proliferation, thereby improving airway hyperresponsiveness and airway remodeling in asthma. Collectively, we conclude that M2 exosomal miR-186-5p to alleviate asthma progression and airway hyperresponsiveness though downregulating TRPP2 expression. These results may offer a novel insight to the treatment and drug delivery of asthma.

Asthma; Exosomes; M2 macrophages; MiR-186-5p; Transient receptor potential polycystic protein 2.