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SIRT1 increases cardiomyocyte binucleation in the heart development
SIRT1 regulates cell senescence. We investigated a novel role of SIRT1 in the regulation of cardiomyocyte terminal differentiation in the developing heart. Retinoic acid (RA)-induced binucleation of H9c2 cells was associated with increased SIRT1 expression. Inhibition of SIRT1 activity or expression...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814276/ https://www.ncbi.nlm.nih.gov/pubmed/29487709 http://dx.doi.org/10.18632/oncotarget.23847 |
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author | Shin, Alexandra N. Han, Limin Dasgupta, Chiranjib Huang, Lei Yang, Shumei Zhang, Lubo |
author_facet | Shin, Alexandra N. Han, Limin Dasgupta, Chiranjib Huang, Lei Yang, Shumei Zhang, Lubo |
author_sort | Shin, Alexandra N. |
collection | PubMed |
description | SIRT1 regulates cell senescence. We investigated a novel role of SIRT1 in the regulation of cardiomyocyte terminal differentiation in the developing heart. Retinoic acid (RA)-induced binucleation of H9c2 cells was associated with increased SIRT1 expression. Inhibition of SIRT1 activity or expression significantly decreased RA-induced binucleation. SIRT1 expression was minimal in the fetal heart and significantly upregulated in the hearts of postnatal day 7 (P7) rat pups. In contrast, heart-specific miR-133a expression was high in the fetal heart but significantly reduced in P7 pup hearts. The miR-133a promoter contains a canonical HRE element and hypoxia upregulated miR-133a gene expression in the heart. SIRT1 mRNA 3′UTR has miR-133a binding sequences and miR-133a and hypoxia suppressed SIRT1 expression in cardiomyocytes. Of importance, inhibition of SIRT1 significantly reduced binucleated cardiomyocytes in the hearts of P7 pups. Taken together, the present study reveals a novel role of SIRT1 and its regulation by miR-133a in cardiomyocyte terminal differentiation of the developing heart, and suggests a potential therapeutic strategy that may impact cardiac function later in life. |
format | Online Article Text |
id | pubmed-5814276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58142762018-02-27 SIRT1 increases cardiomyocyte binucleation in the heart development Shin, Alexandra N. Han, Limin Dasgupta, Chiranjib Huang, Lei Yang, Shumei Zhang, Lubo Oncotarget Research Paper SIRT1 regulates cell senescence. We investigated a novel role of SIRT1 in the regulation of cardiomyocyte terminal differentiation in the developing heart. Retinoic acid (RA)-induced binucleation of H9c2 cells was associated with increased SIRT1 expression. Inhibition of SIRT1 activity or expression significantly decreased RA-induced binucleation. SIRT1 expression was minimal in the fetal heart and significantly upregulated in the hearts of postnatal day 7 (P7) rat pups. In contrast, heart-specific miR-133a expression was high in the fetal heart but significantly reduced in P7 pup hearts. The miR-133a promoter contains a canonical HRE element and hypoxia upregulated miR-133a gene expression in the heart. SIRT1 mRNA 3′UTR has miR-133a binding sequences and miR-133a and hypoxia suppressed SIRT1 expression in cardiomyocytes. Of importance, inhibition of SIRT1 significantly reduced binucleated cardiomyocytes in the hearts of P7 pups. Taken together, the present study reveals a novel role of SIRT1 and its regulation by miR-133a in cardiomyocyte terminal differentiation of the developing heart, and suggests a potential therapeutic strategy that may impact cardiac function later in life. Impact Journals LLC 2018-01-03 /pmc/articles/PMC5814276/ /pubmed/29487709 http://dx.doi.org/10.18632/oncotarget.23847 Text en Copyright: © 2018 Shin et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Shin, Alexandra N. Han, Limin Dasgupta, Chiranjib Huang, Lei Yang, Shumei Zhang, Lubo SIRT1 increases cardiomyocyte binucleation in the heart development |
title | SIRT1 increases cardiomyocyte binucleation in the heart development |
title_full | SIRT1 increases cardiomyocyte binucleation in the heart development |
title_fullStr | SIRT1 increases cardiomyocyte binucleation in the heart development |
title_full_unstemmed | SIRT1 increases cardiomyocyte binucleation in the heart development |
title_short | SIRT1 increases cardiomyocyte binucleation in the heart development |
title_sort | sirt1 increases cardiomyocyte binucleation in the heart development |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814276/ https://www.ncbi.nlm.nih.gov/pubmed/29487709 http://dx.doi.org/10.18632/oncotarget.23847 |
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