LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis.
Bosn J Basic Med Sci
; 22(5): 772-783, 2022 Sep 16.
Article
en En
| MEDLINE
| ID: mdl-35490365
ABSTRACT
The regenerative potential of cardiomyocytes in adult mammals is limited. Previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Miocitos Cardíacos
/
Proteínas Quinasas Activadas por AMP
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Bosn J Basic Med Sci
Asunto de la revista:
MEDICINA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China