Bageghni, SA, Frentzou, GA, Drinkhill, MJ orcid.org/0000-0002-9007-1130 et al. (3 more authors) (2017) Cardiomyocyte specific expression of the nuclear matrix protein, CIZ1, stimulates production of mononucleated cells with an extended window of proliferation in the postnatal mouse heart. Biology Open, 6 (1). pp. 92-99. ISSN 2046-6390
Abstract
Myocardial injury in mammals leads to heart failure through pathological cardiac remodelling that includes hypertrophy, fibrosis and ventricular dilatation. Central to this is inability of the mammalian cardiomyocyte to self-renew due to entering a quiescent state after birth. Modulation of the cardiomyocyte cell-cycle after injury is therefore a target mechanism to limit damage and potentiate repair and regeneration. Here we show that cardiomyocyte specific over-expression of the nuclear-matrix associated DNA replication protein, CIZ1, extends their window of proliferation during cardiac development, delaying onset of terminal differentiation without compromising function. CIZ1 expressing hearts are enlarged, but the cardiomyocytes are smaller with an overall increase in number, correlating with increased DNA replication after birth and retention of an increased proportion of mono-nucleated cardiomyocytes into adulthood. Furthermore, these CIZ1 induced changes in the heart reduce the impact of myocardial injury, identifying CIZ1 as a putative therapeutic target for cardiac repair.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Cardiac function; Cardiomyocyte; CIZ1; DNA replication; Nuclear-matrix protein |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Jan 2017 11:57 |
Last Modified: | 23 Jun 2023 22:20 |
Published Version: | https://doi.org/10.1242/bio.021550 |
Status: | Published |
Publisher: | Company of Biologists |
Identification Number: | 10.1242/bio.021550 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110140 |