Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway

被引:33
|
作者
Yu, Hui [1 ,2 ]
Qin, Lei [3 ]
Peng, Yunzhi [2 ]
Bai, Wenhui [2 ]
Wang, Zhanli [2 ]
机构
[1] Baotou Med Coll, Sch Basic Med, Baotou, Peoples R China
[2] Baotou Med Coll, Inner Mongolia Key Lab Dis Related Biomarkers, Baotou, Peoples R China
[3] Inner Mongolia Maternal & Child Hlth Care Hosp, Genet Eugen Dept, Hohhot, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 11卷
基金
中国国家自然科学基金;
关键词
cardiac hypertrophy; exosome; microRNA; macrophage; inflammation;
D O I
10.3389/fimmu.2020.606045
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The inflammatory immune microenvironment plays an important role in the development of cardiac hypertrophy. Exosomes have emerged as the potent modulators of inflammatory responses. This study aimed to determine how exosomes derived from angiotensin II (Ang II)-induced hypertrophic cardiomyocytes (HCs) interfere with the inflammatory signal pathways in macrophages. Herein, we showed that increased exosome release was observed in HCs when compared to normal cardiomyocytes (NCs). Incubation of the murine macrophage cell line RAW264.7 in the presence of exosomes isolated from the culture media of HCs triggers the secretion of inflammatory cytokines interleukin (IL)-6 and IL-8. Cytokines release induced by HCs-derived exosomes was prevented by down-regulation of Argonaute2 (AGO2), suggesting that the non-coding RNAs were involved in exosome-induced inflammatory responses in RAW 264.7 macrophages. RNA sequencing assays further demonstrated that a total of seven microRNAs were differentially expressed between NCs-derived and HCs-derived exosomes. Importantly, miR-155 played a crucial role in the initiation of inflammation in macrophages. Further analyses demonstrated that HCs-derived exosomes induced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 via miR-155. Our results support the concept that exosomal microRNAs have emerged as important inflammatory response modulators regulating cardiac hypertrophy.
引用
收藏
页数:11
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