M2 macrophage-derived exosomes carry microRNA-370 to alleviate asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.

Abstract Purpose Emerging evidence has suggested the functions of exosomes in allergic diseases including asthma. This work aimed to study the roles of M2 macrophage-derived exosomes (M2Φ-Exos) in pediatric asthma progression and the potential molecules. Methods A mouse model with asthma was induced by ovalbumin (OVA) and treated with M2Φ-Exos. The secretion of inflammatory cytokines, fibrosis and inflammatory cell infiltration in mouse lung tissues were determined. The number of granulocytes in bronchoalveolar lavage fluid was measured. Airway epithelial cells (AECs) were treated with PDGF-BB for in vitro experiments. Proliferation, invasion, migration abilities and the expression of inflammation- and fibrosis-related factors in AECs were detected. Differentially expressed miRNAs after M2Φ-Exo treatment were screened out using a miRNA microarray. Targeting mRNAs of miR-370 were predicted on bioinformatics systems. Altered expression of miR-370 or FGF1 was introduced in mouse and cell models to validate their functions in asthma progression. Results M2Φ-Exos significantly alleviated OVA-induced fibrosis and inflammatory responses in mouse lung tissues, and inhibited abnormal proliferation and invasion, and fibrosis-related cytokine production in PDGF-BB-treated AECs. miR-370 was significantly upregulated after M2-exo treatment. FGF1 was identified as a target of miR-370. Knockdown of miR-370 or overexpression of FGF1 blocked the protective roles of M2Φ-Exos in mouse and cell models. M2Φ-Exos were found to inactivate the MAPK signaling pathway, which was recovered by further miR-370 inhibition or FGF1 overexpression. Conclusion M2Φ-Exos carry miR-370 to alleviate asthma progression through downregulating FGF1 and the MAPK/STAT1 signaling pathway. This study may offer novel insights into asthma treatment.