Cargando…

Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration

The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Wei, Feng, Yuliang, Liang, Jialiang, Yu, Hao, Wang, Cheng, Wang, Boyu, Wang, Mingyang, Jiang, Lin, Meng, Wei, Cai, Wenfeng, Medvedovic, Mario, Chen, Jenny, Paul, Christian, Davidson, W. Sean, Sadayappan, Sakthivel, Stambrook, Peter J., Yu, Xi-Yong, Wang, Yigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816015/
https://www.ncbi.nlm.nih.gov/pubmed/29453456
http://dx.doi.org/10.1038/s41467-018-03019-z
_version_ 1783300597054701568
author Huang, Wei
Feng, Yuliang
Liang, Jialiang
Yu, Hao
Wang, Cheng
Wang, Boyu
Wang, Mingyang
Jiang, Lin
Meng, Wei
Cai, Wenfeng
Medvedovic, Mario
Chen, Jenny
Paul, Christian
Davidson, W. Sean
Sadayappan, Sakthivel
Stambrook, Peter J.
Yu, Xi-Yong
Wang, Yigang
author_facet Huang, Wei
Feng, Yuliang
Liang, Jialiang
Yu, Hao
Wang, Cheng
Wang, Boyu
Wang, Mingyang
Jiang, Lin
Meng, Wei
Cai, Wenfeng
Medvedovic, Mario
Chen, Jenny
Paul, Christian
Davidson, W. Sean
Sadayappan, Sakthivel
Stambrook, Peter J.
Yu, Xi-Yong
Wang, Yigang
author_sort Huang, Wei
collection PubMed
description The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR-128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of fibrosis, and attenuating cardiac dysfunction in response to MI. These results suggest that miR-128 serves as a critical regulator of endogenous CM proliferation, and might be a novel therapeutic target for heart repair.
format Online
Article
Text
id pubmed-5816015
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-58160152018-02-20 Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration Huang, Wei Feng, Yuliang Liang, Jialiang Yu, Hao Wang, Cheng Wang, Boyu Wang, Mingyang Jiang, Lin Meng, Wei Cai, Wenfeng Medvedovic, Mario Chen, Jenny Paul, Christian Davidson, W. Sean Sadayappan, Sakthivel Stambrook, Peter J. Yu, Xi-Yong Wang, Yigang Nat Commun Article The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR-128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of fibrosis, and attenuating cardiac dysfunction in response to MI. These results suggest that miR-128 serves as a critical regulator of endogenous CM proliferation, and might be a novel therapeutic target for heart repair. Nature Publishing Group UK 2018-02-16 /pmc/articles/PMC5816015/ /pubmed/29453456 http://dx.doi.org/10.1038/s41467-018-03019-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Huang, Wei
Feng, Yuliang
Liang, Jialiang
Yu, Hao
Wang, Cheng
Wang, Boyu
Wang, Mingyang
Jiang, Lin
Meng, Wei
Cai, Wenfeng
Medvedovic, Mario
Chen, Jenny
Paul, Christian
Davidson, W. Sean
Sadayappan, Sakthivel
Stambrook, Peter J.
Yu, Xi-Yong
Wang, Yigang
Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title_full Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title_fullStr Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title_full_unstemmed Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title_short Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
title_sort loss of microrna-128 promotes cardiomyocyte proliferation and heart regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816015/
https://www.ncbi.nlm.nih.gov/pubmed/29453456
http://dx.doi.org/10.1038/s41467-018-03019-z
work_keys_str_mv AT huangwei lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT fengyuliang lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT liangjialiang lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT yuhao lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT wangcheng lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT wangboyu lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT wangmingyang lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT jianglin lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT mengwei lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT caiwenfeng lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT medvedovicmario lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT chenjenny lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT paulchristian lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT davidsonwsean lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT sadayappansakthivel lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT stambrookpeterj lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT yuxiyong lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration
AT wangyigang lossofmicrorna128promotescardiomyocyteproliferationandheartregeneration