miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy

Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2-Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-...

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הוצא לאור ב:PLoS One
Main Authors: Clark, Amanda L., Maruyama, Sonomi, Sano, Soichi, Accorsi, Anthony, Girgenrath, Mahasweta, Walsh, Kenneth, Naya, Francisco J.
פורמט: Artigo
שפה:Inglês
יצא לאור: Public Library of Science 2016
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Research Article
גישה מקוונת:https://ncbi.nlm.nih.gov/pmc/articles/PMC4801331/
https://ncbi.nlm.nih.gov/pubmed/26999812
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1371/journal.pone.0151515
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spelling pubmed-48013312016-03-23 miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy Clark, Amanda L. Maruyama, Sonomi Sano, Soichi Accorsi, Anthony Girgenrath, Mahasweta Walsh, Kenneth Naya, Francisco J. PLoS One Research Article Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2-Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-495, induce robust cardiomyocyte proliferation. Given the possibility of manipulating the expression of these miRNAs to repair the damaged heart by stimulating cardiomyocyte proliferation, it is important to determine whether the Gtl2-Dio3 noncoding RNAs are regulated in cardiac disease and whether they function downstream of pathological cardiac stress signaling. Therefore, we examined expression of the above miRNAs processed from the Gtl2-Dio3 locus in various cardiomyopathies. These noncoding RNAs were upregulated in all cardiac disease models examined including myocardial infarction (MI) and chronic angiotensin II (Ang II) stimulation, and in the cardiomyopathies associated with muscular dystrophies. Consistent with these observations, we show that the Gtl2-Dio3 proximal promoter is activated by stress stimuli in cardiomyocytes and requires MEF2 for its induction. Furthermore, inhibiting miR-410 or miR-495 in stressed cardiomyocytes attenuated the hypertrophic response. Thus, the Gtl2-Dio3 noncoding RNA locus is a novel marker of cardiac disease and modulating the activity of its encoded miRNAs may mitigate pathological cardiac remodeling in these diseases. Public Library of Science 2016-03-21 /pmc/articles/PMC4801331/ /pubmed/26999812 http://dx.doi.org/10.1371/journal.pone.0151515 Text en © 2016 Clark 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.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Research Article
spellingShingle Research Article
Clark, Amanda L.
Maruyama, Sonomi
Sano, Soichi
Accorsi, Anthony
Girgenrath, Mahasweta
Walsh, Kenneth
Naya, Francisco J.
miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
description Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2-Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-495, induce robust cardiomyocyte proliferation. Given the possibility of manipulating the expression of these miRNAs to repair the damaged heart by stimulating cardiomyocyte proliferation, it is important to determine whether the Gtl2-Dio3 noncoding RNAs are regulated in cardiac disease and whether they function downstream of pathological cardiac stress signaling. Therefore, we examined expression of the above miRNAs processed from the Gtl2-Dio3 locus in various cardiomyopathies. These noncoding RNAs were upregulated in all cardiac disease models examined including myocardial infarction (MI) and chronic angiotensin II (Ang II) stimulation, and in the cardiomyopathies associated with muscular dystrophies. Consistent with these observations, we show that the Gtl2-Dio3 proximal promoter is activated by stress stimuli in cardiomyocytes and requires MEF2 for its induction. Furthermore, inhibiting miR-410 or miR-495 in stressed cardiomyocytes attenuated the hypertrophic response. Thus, the Gtl2-Dio3 noncoding RNA locus is a novel marker of cardiac disease and modulating the activity of its encoded miRNAs may mitigate pathological cardiac remodeling in these diseases.
author Clark, Amanda L.
Maruyama, Sonomi
Sano, Soichi
Accorsi, Anthony
Girgenrath, Mahasweta
Walsh, Kenneth
Naya, Francisco J.
author_facet Clark, Amanda L.
Maruyama, Sonomi
Sano, Soichi
Accorsi, Anthony
Girgenrath, Mahasweta
Walsh, Kenneth
Naya, Francisco J.
author_sort Clark, Amanda L.
title miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
title_short miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
title_full miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
title_fullStr miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
title_full_unstemmed miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy
title_sort mir-410 and mir-495 are dynamically regulated in diverse cardiomyopathies and their inhibition attenuates pathological hypertrophy
publisher Public Library of Science
container_title PLoS One
publishDate 2016
url https://ncbi.nlm.nih.gov/pmc/articles/PMC4801331/
https://ncbi.nlm.nih.gov/pubmed/26999812
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1371/journal.pone.0151515
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