CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1α pathway.
Exp Cell Res
; 405(2): 112730, 2021 08 15.
Article
en En
| MEDLINE
| ID: mdl-34242624
ABSTRACT
CBL (Casitas B cell lymphoma), an important ubiquitin protein ligase, is involved in protein folding, protein maturation, and proteasome-dependent protein catabolism in different cells. However, its role in cardiac hypertrophy is still unclear. In this study, we found that expression of CBL is increased in an Ang II-induced mouse cardiac hypertrophy animal model and in Ang II-treated H9C2 cells. Interference with CBL expression attenuates the degree of myocardial hypertrophy as well as the expression of hypertrophy-related genes in H9C2 cells. Further research found that CBL aggravates myocardial hypertrophy by activating HIF-1α, which is an aggravating factor for hypertrophy. The effect of CBL on promoting myocardial hypertrophy was reversed by interference with HIF-1α. Mechanistically, we found that CBL directly interacted with and degraded VHL by increasing its ubiquitination level, which is a widely accepted regulatory factor of HIF-1α. Finally, our results showed that CBL was partially dependent on degradation of VHL and that activation of HIF-1α promoted myocardial hypertrophy. Collectively, these findings suggest that strategies based on activation of the CBL/HIF-1α axis might be promising for the treatment of hypertrophic cardiomyopathy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfoma de Células B
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Cardiomegalia
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Ubiquitina-Proteína Ligasas
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Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau
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Subunidad alfa del Factor 1 Inducible por Hipoxia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article