Int J Biol Sci 2021; 17(7):1795-1807. doi:10.7150/ijbs.59715

Research Paper

MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis

Chunlu Li1, Chengsi Deng2, Tingting Zhou2, Jiapeng Hu1, Bing Dai1, Fei Yi2, Na Tian3, Lijun Jiang3, Xiang Dong2, Qingfeng Zhu2, Siyi Zhang2, Hongyan Cui2, Liu Cao2✉, Yunxiao Shang1✉

1. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
2. College of Basic Medicine Science, China Medical University, Shenyang 110122, China.
3. Jilin Tuohua Biotechnology Co., Ltd. Changchun, Jilin 13000, China.

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Citation:
Li C, Deng C, Zhou T, Hu J, Dai B, Yi F, Tian N, Jiang L, Dong X, Zhu Q, Zhang S, Cui H, Cao L, Shang Y. MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis. Int J Biol Sci 2021; 17(7):1795-1807. doi:10.7150/ijbs.59715. Available from https://www.ijbs.com/v17p1795.htm

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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.

Keywords: M2 macrophages, exosomes, miR-370, FGF1, asthma