期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 17, 期 7, 页码 1795-1807出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.59715
关键词
M2 macrophages; exosomes; miR-370; FGF1; asthma
The study revealed that M2 macrophagederived exosomes can alleviate asthma progression by downregulating FGF1 expression and the MAPK/STAT1 signaling pathway through carrying miR-370. This mechanism provides a new perspective for asthma treatment.
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 macrophagederived exosomes (M20-Exos) in asthma progression. M20-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 M20-Exos by miRNA sequencing. However, treating the mice or ASMCs with M20-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 M20-Exos in asthma-like mouse and cell models. M20-Exos were found to inactivate the MAPK signaling pathway, which was recovered by miR-370 inhibition or FGF1 overexpression. Collectively, we conclude that M20-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.
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