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Filamin C is Essential for mammalian myocardial integrity
FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (Flnc(gKO)) and cardiomyocyte-specific knockout (Flnc(cKO)) mice died in utero...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907827/ https://www.ncbi.nlm.nih.gov/pubmed/36706168 http://dx.doi.org/10.1371/journal.pgen.1010630 |
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author | Wu, Tongbin Xu, Yujun Zhang, Lunfeng Liang, Zhengyu Zhou, Xiaohai Evans, Sylvia M. Chen, Ju |
author_facet | Wu, Tongbin Xu, Yujun Zhang, Lunfeng Liang, Zhengyu Zhou, Xiaohai Evans, Sylvia M. Chen, Ju |
author_sort | Wu, Tongbin |
collection | PubMed |
description | FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (Flnc(gKO)) and cardiomyocyte-specific knockout (Flnc(cKO)) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of β1 integrin specifically in the myocardium of Flnc(gKO) mice. Although deleting β1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both β1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with β1 integrin to maintain the structural integrity of myocardium during mammalian heart development. |
format | Online Article Text |
id | pubmed-9907827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99078272023-02-08 Filamin C is Essential for mammalian myocardial integrity Wu, Tongbin Xu, Yujun Zhang, Lunfeng Liang, Zhengyu Zhou, Xiaohai Evans, Sylvia M. Chen, Ju PLoS Genet Research Article FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (Flnc(gKO)) and cardiomyocyte-specific knockout (Flnc(cKO)) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of β1 integrin specifically in the myocardium of Flnc(gKO) mice. Although deleting β1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both β1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with β1 integrin to maintain the structural integrity of myocardium during mammalian heart development. Public Library of Science 2023-01-27 /pmc/articles/PMC9907827/ /pubmed/36706168 http://dx.doi.org/10.1371/journal.pgen.1010630 Text en © 2023 Wu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 Wu, Tongbin Xu, Yujun Zhang, Lunfeng Liang, Zhengyu Zhou, Xiaohai Evans, Sylvia M. Chen, Ju Filamin C is Essential for mammalian myocardial integrity |
title | Filamin C is Essential for mammalian myocardial integrity |
title_full | Filamin C is Essential for mammalian myocardial integrity |
title_fullStr | Filamin C is Essential for mammalian myocardial integrity |
title_full_unstemmed | Filamin C is Essential for mammalian myocardial integrity |
title_short | Filamin C is Essential for mammalian myocardial integrity |
title_sort | filamin c is essential for mammalian myocardial integrity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907827/ https://www.ncbi.nlm.nih.gov/pubmed/36706168 http://dx.doi.org/10.1371/journal.pgen.1010630 |
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