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miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787679/ https://www.ncbi.nlm.nih.gov/pubmed/33351798 http://dx.doi.org/10.1371/journal.pntd.0008889 |
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author | Laugier, Laurie Ferreira, Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Cabantous, Sandrine Frade, Amanda Farage Nunes, Joao Paulo Ribeiro, Rafael Almeida Brochet, Pauline Teixeira, Priscila Camillo Santos, Ronaldo Honorato Barros Bocchi, Edimar A. Bacal, Fernando Cândido, Darlan da Silva Maso, Vanessa Escolano Nakaya, Helder I. Kalil, Jorge Cunha-Neto, Edecio Chevillard, Christophe |
author_facet | Laugier, Laurie Ferreira, Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Cabantous, Sandrine Frade, Amanda Farage Nunes, Joao Paulo Ribeiro, Rafael Almeida Brochet, Pauline Teixeira, Priscila Camillo Santos, Ronaldo Honorato Barros Bocchi, Edimar A. Bacal, Fernando Cândido, Darlan da Silva Maso, Vanessa Escolano Nakaya, Helder I. Kalil, Jorge Cunha-Neto, Edecio Chevillard, Christophe |
author_sort | Laugier, Laurie |
collection | PubMed |
description | Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy. |
format | Online Article Text |
id | pubmed-7787679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77876792021-01-14 miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy Laugier, Laurie Ferreira, Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Cabantous, Sandrine Frade, Amanda Farage Nunes, Joao Paulo Ribeiro, Rafael Almeida Brochet, Pauline Teixeira, Priscila Camillo Santos, Ronaldo Honorato Barros Bocchi, Edimar A. Bacal, Fernando Cândido, Darlan da Silva Maso, Vanessa Escolano Nakaya, Helder I. Kalil, Jorge Cunha-Neto, Edecio Chevillard, Christophe PLoS Negl Trop Dis Research Article Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy. Public Library of Science 2020-12-22 /pmc/articles/PMC7787679/ /pubmed/33351798 http://dx.doi.org/10.1371/journal.pntd.0008889 Text en © 2020 Laugier et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Laugier, Laurie Ferreira, Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Cabantous, Sandrine Frade, Amanda Farage Nunes, Joao Paulo Ribeiro, Rafael Almeida Brochet, Pauline Teixeira, Priscila Camillo Santos, Ronaldo Honorato Barros Bocchi, Edimar A. Bacal, Fernando Cândido, Darlan da Silva Maso, Vanessa Escolano Nakaya, Helder I. Kalil, Jorge Cunha-Neto, Edecio Chevillard, Christophe miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title | miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title_full | miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title_fullStr | miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title_full_unstemmed | miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title_short | miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy |
title_sort | mirnas may play a major role in the control of gene expression in key pathobiological processes in chagas disease cardiomyopathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787679/ https://www.ncbi.nlm.nih.gov/pubmed/33351798 http://dx.doi.org/10.1371/journal.pntd.0008889 |
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