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MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the
Chunlu Li1, Chengsi Deng2, Tingting Zhou2
1Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Abstract:
Emerging evidence has suggested the functions of exosomes in allergic diseases including asthma. By using a mouse model with asthma induced by ovalbumin (OVA), we explored the roles of M2 macrophage-derived exosomes (M2Φ-Exos) in asthma progression. M2Φ-Exos significantly alleviated OVA-induced fibrosis and inflammatory responses in mouse lung tissues, as well as inhibited abnormal proliferation, invasion, and fibrosis-related protein production in platelet derived growth factor (PDGF-BB) treated primary mouse airway smooth muscle cells (ASMCs). The OVA administration in mice or the PDGF-BB treatment in ASMCs reduced the expression of miR-370, which was detected in M2Φ-Exos by miRNA sequencing. However, treating the mice or ASMCs with M2Φ-Exos reversed the inhibitory effect of OVA or PDGF-BB on miR-370 expression. We identified that the target of miR-370 was fibroblast growth factor 1 (FGF1). Downregulation of miR-370 by Lv-miR-370 inhibitor or overexpression of FGF1 by Lv-FGF1 blocked the protective roles of M2Φ-Exos in asthma-like mouse and cell models. M2Φ-Exos were found to inactivate the MAPK signaling pathway, which was recovered by miR-370 inhibition or FGF1 overexpression. Collectively, we conclude that M2Φ-Exos carry miR-370 to alleviate asthma progression through downregulating FGF1 expression and the MAPK/STAT1 signaling pathway. Our study may offer a novel insight into asthma treatment.
Insights
M2 macrophage-derived exosomes (M2Φ-Exos) alleviate asthma by delivering miR-370, which targets fibroblast growth factor 1 (FGF1). This process inhibits airway smooth muscle cell proliferation and inflammation, offering a potential new asthma treatment.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Exosomes play roles in allergic diseases like asthma.
- Understanding exosome function in asthma progression is crucial for developing new therapies.
Purpose of the Study:
- To investigate the role of M2 macrophage-derived exosomes (M2Φ-Exos) in asthma.
- To elucidate the molecular mechanisms by which M2Φ-Exos exert protective effects in asthma.
Main Methods:
- Ovalbumin (OVA)-induced asthma mouse model.
- Primary mouse airway smooth muscle cells (ASMCs) treated with platelet-derived growth factor (PDGF-BB).
- miRNA sequencing, gene silencing, and overexpression techniques.
Main Results:
- M2Φ-Exos reduced lung fibrosis and inflammation in asthma models.
- M2Φ-Exos inhibited ASMC proliferation, invasion, and fibrosis-related protein production.
- M2Φ-Exos delivered miR-370, targeting FGF1 and inactivating the MAPK signaling pathway.
Conclusions:
- M2Φ-Exos alleviate asthma progression by downregulating FGF1 via miR-370.
- The mechanism involves the MAPK/STAT1 signaling pathway.
- M2Φ-Exos represent a potential therapeutic strategy for asthma.
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