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Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway
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 (H...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886800/ https://www.ncbi.nlm.nih.gov/pubmed/33613526 http://dx.doi.org/10.3389/fimmu.2020.606045 |
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author | Yu, Hui Qin, Lei Peng, Yunzhi Bai, Wenhui Wang, Zhanli |
author_facet | Yu, Hui Qin, Lei Peng, Yunzhi Bai, Wenhui Wang, Zhanli |
author_sort | Yu, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7886800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78868002021-02-18 Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway Yu, Hui Qin, Lei Peng, Yunzhi Bai, Wenhui Wang, Zhanli Front Immunol Immunology 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. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7886800/ /pubmed/33613526 http://dx.doi.org/10.3389/fimmu.2020.606045 Text en Copyright © 2021 Yu, Qin, Peng, Bai and Wang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yu, Hui Qin, Lei Peng, Yunzhi Bai, Wenhui Wang, Zhanli Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title | Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title_full | Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title_fullStr | Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title_full_unstemmed | Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title_short | Exosomes Derived From Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway |
title_sort | exosomes derived from hypertrophic cardiomyocytes induce inflammation in macrophages via mir-155 mediated mapk pathway |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886800/ https://www.ncbi.nlm.nih.gov/pubmed/33613526 http://dx.doi.org/10.3389/fimmu.2020.606045 |
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