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Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome
BACKGROUND: Viral myocarditis (VMC) is a type of cardiac inflammation that is generally caused by coxsackievirus B3 (CVB3) infection. Several MicroRNAs (miRNAs) are known to play crucial roles in VMC pathogenesis. MiR-15 is reportedly associated with myocardial injury, inflammatory responses and vir...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031959/ https://www.ncbi.nlm.nih.gov/pubmed/32099552 http://dx.doi.org/10.1186/s11658-020-00203-2 |
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author | Tong, Ru Jia, Tiewen Shi, Ruijie Yan, Futang |
author_facet | Tong, Ru Jia, Tiewen Shi, Ruijie Yan, Futang |
author_sort | Tong, Ru |
collection | PubMed |
description | BACKGROUND: Viral myocarditis (VMC) is a type of cardiac inflammation that is generally caused by coxsackievirus B3 (CVB3) infection. Several MicroRNAs (miRNAs) are known to play crucial roles in VMC pathogenesis. MiR-15 is reportedly associated with myocardial injury, inflammatory responses and viral infection. Whether miR-15 affects the occurrence and development of VMC remains largely unknown. The roles of miR-15 and their underlying mechanisms in CVB3-stimulated H9c2 cells were assessed in this study. METHODS: We infected H9c2 cells with CVB3 to establish a VMC cellular model. We then determined the effects of miR-15 inhibition on three cardiomyocyte injury markers: lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I). The impact on CVB3-induced cell apoptosis and pro-inflammatory cytokines was also investigated. The effects of miR-15 inhibition on NLRP3 inflammasome activation were also assessed. The target relationship between miR-15 and NOD-like receptor X1 (NLRX1) was determined using a luciferase reporter assay. RESULTS: MiR-15 expression was significantly upregulated in H9c2 cells after CVB3 infection. Inhibition of miR-15 significantly decreased the CVB3-induced levels of LDH, CK-MB and cTn-I. It also elevated cell viability, reduced CVB3-induced cell apoptosis and decreased the generation of the interleukins IL-1β, IL-6 and IL-18. Furthermore, we determined that miR-15 inhibition suppressed NLRP3 inflammasome activation by downregulating NLRP3 and caspase-1 p20 expression. We found a direct target relationship between miR-15 and NLRX1. Additionally, inhibition of NLRX1 reversed the protective effects of miR-15 inhibition against CVB3-induced myocardial cell injury by regulating the NLRP3 inflammasome. CONCLUSION: Our results indicate that miR-15 inhibition alleviates CVB3-induced myocardial inflammation and cell injury. This may be partially due to NLRX1-mediated NLRP3 inflammasome inactivation. |
format | Online Article Text |
id | pubmed-7031959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70319592020-02-25 Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome Tong, Ru Jia, Tiewen Shi, Ruijie Yan, Futang Cell Mol Biol Lett Research BACKGROUND: Viral myocarditis (VMC) is a type of cardiac inflammation that is generally caused by coxsackievirus B3 (CVB3) infection. Several MicroRNAs (miRNAs) are known to play crucial roles in VMC pathogenesis. MiR-15 is reportedly associated with myocardial injury, inflammatory responses and viral infection. Whether miR-15 affects the occurrence and development of VMC remains largely unknown. The roles of miR-15 and their underlying mechanisms in CVB3-stimulated H9c2 cells were assessed in this study. METHODS: We infected H9c2 cells with CVB3 to establish a VMC cellular model. We then determined the effects of miR-15 inhibition on three cardiomyocyte injury markers: lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I). The impact on CVB3-induced cell apoptosis and pro-inflammatory cytokines was also investigated. The effects of miR-15 inhibition on NLRP3 inflammasome activation were also assessed. The target relationship between miR-15 and NOD-like receptor X1 (NLRX1) was determined using a luciferase reporter assay. RESULTS: MiR-15 expression was significantly upregulated in H9c2 cells after CVB3 infection. Inhibition of miR-15 significantly decreased the CVB3-induced levels of LDH, CK-MB and cTn-I. It also elevated cell viability, reduced CVB3-induced cell apoptosis and decreased the generation of the interleukins IL-1β, IL-6 and IL-18. Furthermore, we determined that miR-15 inhibition suppressed NLRP3 inflammasome activation by downregulating NLRP3 and caspase-1 p20 expression. We found a direct target relationship between miR-15 and NLRX1. Additionally, inhibition of NLRX1 reversed the protective effects of miR-15 inhibition against CVB3-induced myocardial cell injury by regulating the NLRP3 inflammasome. CONCLUSION: Our results indicate that miR-15 inhibition alleviates CVB3-induced myocardial inflammation and cell injury. This may be partially due to NLRX1-mediated NLRP3 inflammasome inactivation. BioMed Central 2020-02-19 /pmc/articles/PMC7031959/ /pubmed/32099552 http://dx.doi.org/10.1186/s11658-020-00203-2 Text en © The Author(s) 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Tong, Ru Jia, Tiewen Shi, Ruijie Yan, Futang Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title | Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title_full | Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title_fullStr | Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title_full_unstemmed | Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title_short | Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome |
title_sort | inhibition of microrna-15 protects h9c2 cells against cvb3-induced myocardial injury by targeting nlrx1 to regulate the nlrp3 inflammasome |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031959/ https://www.ncbi.nlm.nih.gov/pubmed/32099552 http://dx.doi.org/10.1186/s11658-020-00203-2 |
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