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

Jiaying Yuan1,2, Jiayi Zhao3, Xiahui Ge4

  • 1Department of General Practice, Shanghai Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China, chhospital.com.cn.

PubMed
Abstract

Insights

M2 macrophage-derived exosomes, enriched with circ-Eif3c, show therapeutic potential for asthma by reducing lung inflammation and injury. These exosomes restore alveolar epithelial cell function, offering a novel treatment strategy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling.
  • Macrophage-derived exosomes are implicated in intercellular communication and immune responses.
  • M2 macrophages play a role in immune regulation and tissue repair.

Purpose of the Study:

  • To investigate the therapeutic mechanisms of M2 macrophage-derived exosomes in asthma.
  • To identify key molecular players involved in the exosome-mediated therapeutic effects.
  • To elucidate the regulatory network involving circRNAs, microRNAs, and target genes.

Main Methods:

  • Isolation of exosomes from M0 and M2 macrophages.
  • Establishment of an ovalbumin (OVA)-induced asthma mouse model and lipopolysaccharide (LPS)-induced alveolar epithelial cells (AECs).
  • High-throughput sequencing for circRNA identification, followed by bioinformatic and luciferase reporter assays.

Main Results:

  • M2 macrophage-derived exosomes (M2Φ-Exos) suppressed OVA-induced inflammation and lung injury.
  • Circ-Eif3c was upregulated in M2Φ-Exos and its downregulation impaired therapeutic effects.
  • Circ-Eif3c targeted miR-15a-5p, regulating glutathione synthetase (GSS) and suppressor of cytokine signaling 6 (SOCS6) expression.

Conclusions:

  • Circ-Eif3c-enriched M2Φ-Exos attenuate airway remodeling by restoring AEC function.
  • The circ-Eif3c/miR-15a-5p/GSS/SOCS6 axis is a key mechanism in M2Φ-Exos therapy for asthma.
  • M2Φ-Exos represent a promising therapeutic strategy for asthma treatment.

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