Cargando…

miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage

Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Jiwen, Jiang, Mei, Deng, Shengqiong, Lu, Jide, Huang, Hui, Zhang, Yu, Gong, Peihua, Shen, Xumin, Ruan, Huanjun, Jin, Mingming, Wang, Hairong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852413/
https://www.ncbi.nlm.nih.gov/pubmed/29858047
http://dx.doi.org/10.1016/j.omtn.2018.01.010
_version_ 1783306566649249792
author Liu, Jiwen
Jiang, Mei
Deng, Shengqiong
Lu, Jide
Huang, Hui
Zhang, Yu
Gong, Peihua
Shen, Xumin
Ruan, Huanjun
Jin, Mingming
Wang, Hairong
author_facet Liu, Jiwen
Jiang, Mei
Deng, Shengqiong
Lu, Jide
Huang, Hui
Zhang, Yu
Gong, Peihua
Shen, Xumin
Ruan, Huanjun
Jin, Mingming
Wang, Hairong
author_sort Liu, Jiwen
collection PubMed
description Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective effect after acute myocardial infarction (AMI). To identify whether miR-93-5p-encapsulating exosomes that form ADSCs have a better cardio-protective effect, we investigated the inflammatory factors and miR-30d-5p expression in clinical levels. A rat model of AMI and an in vitro model of hypoxic H9c2 cells were established to study the protective mechanism of miR-93-5p in ischemia-induced cardiac injury. The results show that the expression of inflammatory cytokines and miR-93-5p were increased following AMI in both patients and animal models. Moreover, treatment with ADSC-derived miR-93-5p-containing exosomes has a greater protective effect on infarction-induced myocardial damage than simple exosome processing. Furthermore, in vitro experiments confirmed that the expression of miR-93-5p can significantly suppress hypoxia-induced autophagy and inflammatory cytokine expression by targeting Atg7 and Toll-like receptor 4 (TLR4), respectively, and was confirmed with Atg7 or TLR4 overexpression. The results also show that autophagy activation can promote inflammatory cytokine expression indirectly. Taken together, these results suggest that the miR-93-5p-enhanced ADSC-derived exosomes prevent cardiac injury by inhibiting autophagy and the inflammatory response.
format Online
Article
Text
id pubmed-5852413
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher American Society of Gene & Cell Therapy
record_format MEDLINE/PubMed
spelling pubmed-58524132018-03-16 miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage Liu, Jiwen Jiang, Mei Deng, Shengqiong Lu, Jide Huang, Hui Zhang, Yu Gong, Peihua Shen, Xumin Ruan, Huanjun Jin, Mingming Wang, Hairong Mol Ther Nucleic Acids Article Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective effect after acute myocardial infarction (AMI). To identify whether miR-93-5p-encapsulating exosomes that form ADSCs have a better cardio-protective effect, we investigated the inflammatory factors and miR-30d-5p expression in clinical levels. A rat model of AMI and an in vitro model of hypoxic H9c2 cells were established to study the protective mechanism of miR-93-5p in ischemia-induced cardiac injury. The results show that the expression of inflammatory cytokines and miR-93-5p were increased following AMI in both patients and animal models. Moreover, treatment with ADSC-derived miR-93-5p-containing exosomes has a greater protective effect on infarction-induced myocardial damage than simple exosome processing. Furthermore, in vitro experiments confirmed that the expression of miR-93-5p can significantly suppress hypoxia-induced autophagy and inflammatory cytokine expression by targeting Atg7 and Toll-like receptor 4 (TLR4), respectively, and was confirmed with Atg7 or TLR4 overexpression. The results also show that autophagy activation can promote inflammatory cytokine expression indirectly. Taken together, these results suggest that the miR-93-5p-enhanced ADSC-derived exosomes prevent cardiac injury by inhibiting autophagy and the inflammatory response. American Society of Gene & Cell Therapy 2018-01-31 /pmc/articles/PMC5852413/ /pubmed/29858047 http://dx.doi.org/10.1016/j.omtn.2018.01.010 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Liu, Jiwen
Jiang, Mei
Deng, Shengqiong
Lu, Jide
Huang, Hui
Zhang, Yu
Gong, Peihua
Shen, Xumin
Ruan, Huanjun
Jin, Mingming
Wang, Hairong
miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title_full miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title_fullStr miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title_full_unstemmed miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title_short miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage
title_sort mir-93-5p-containing exosomes treatment attenuates acute myocardial infarction-induced myocardial damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852413/
https://www.ncbi.nlm.nih.gov/pubmed/29858047
http://dx.doi.org/10.1016/j.omtn.2018.01.010
work_keys_str_mv AT liujiwen mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT jiangmei mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT dengshengqiong mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT lujide mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT huanghui mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT zhangyu mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT gongpeihua mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT shenxumin mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT ruanhuanjun mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT jinmingming mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage
AT wanghairong mir935pcontainingexosomestreatmentattenuatesacutemyocardialinfarctioninducedmyocardialdamage