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. 2026 Mar 2:2026:8350424.
doi: 10.1155/mi/8350424. eCollection 2026.

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

Jiaying Yuan  1   2 , Jiayi Zhao  3 , Xiahui Ge  4 , Xingxing Zhu  5 , Li Li  2 , Haoran Ni  2 , Jian Fan  1 , Yi Zhang  1 , Yahong Sun  5 , Yan Shang  1   2
Affiliations

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

Jiaying Yuan et al. Mediators Inflamm. .

Abstract

Background: In the study, we aimed to uncover potential therapeutic mechanisms concerning M2 macrophage-derived exosomes in asthma.

Methods: 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).

Results: 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.

Conclusion: In conclusion, circ-Eif3c-enriched M2Φ-Exos attenuated airway remodeling by restoring the function of AECs.

Keywords: M2 macrophage; asthma; circ-Eif3c; exosome; miR-15a-5p.

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Conflict of interest statement

The authors declare no conflicts of interest.

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Figure 7
Figure 7
Mechanism diagram of circ‐Eif3c carried by M2 macrophage‐derived exosomes attenuated airway remodeling.
See this image and copyright information in PMC

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