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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...

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Autores principales: Wu, Tongbin, Xu, Yujun, Zhang, Lunfeng, Liang, Zhengyu, Zhou, Xiaohai, Evans, Sylvia M., Chen, Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
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.
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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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