Filamin C is Essential for mammalian myocardial integrity.
PLoS Genet
; 19(1): e1010630, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36706168
ABSTRACT
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 (FlncgKO) and cardiomyocyte-specific knockout (FlnccKO) 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 ß1 integrin specifically in the myocardium of FlncgKO mice. Although deleting ß1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both ß1 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 ß1 integrin to maintain the structural integrity of myocardium during mammalian heart development.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Integrina beta1
/
Filaminas
/
Miocardio
Límite:
Animals
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos