Circ-Eif3c Carried by M2 Macrophage-Derived Exosomes Mitigates Asthma Progression via miR-15a-5p/GSS/SOCS6 Axis Inhibition.

In the study, we aimed to uncover potential therapeutic mechanisms concerning M2 macrophage-derived exosomes in asthma. Exosomes were isolated from M0Φ-Exos and M2Φ-Exos. An ovalbumin (OVA)-induced asthma mouse model or lipopolysaccharide (LPS)-induced alveolar epithelial cells (AECs) were created to unravel the therapeutic mechanisms. High-throughput sequencing was used to search for differentially expressed circRNA. Bioinformation analysis and luciferase report analysis were used to reveal the regulationship among circ-Eif3c, miR-15a-5p, glutathione synthetase (GSS), and suppressor of cytokine signaling 6 (SOCS6). The results showed that M2Φ-Exos suppressed OVA-induced inflammatory cytokine secretion and lung injury in mice. Next-generation sequencing (NGS) showed that circ-Eif3c was upregulated in M2Φ-Exos. Circ-Eif3c downregulation inhibited the therapeutic effect of M2Φ-Exos. Bioinformation analysis confirmed that miR-15a-5p, GSS, and SOCS6 were the downstream targets of circ-Eif3c, which were confirmed by luciferase report analysis. The overexpression of miR-15a-5p or the downregulation of GSS/SOCS6 reversed circ-Eif3c's protective effects on LPS-induced AEC damage. The overexpression of circ-Eif3c increased the therapeutic effect of M2Φ-Exos. In conclusion, circ-Eif3c-enriched M2Φ-Exos attenuated airway remodeling by restoring the function of AECs.