Leu promotes C2C12 cell differentiation by regulating the GSK3ß/ß-catenin signaling pathway through facilitating the interaction between SESN2 and RPN2.
J Sci Food Agric
; 104(11): 6696-6705, 2024 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-38551359
ABSTRACT
BACKGROUND:
Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment.RESULTS:
Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3ß and increased nuclear ß-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3ß and decreased nuclear ß-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear ß-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells.CONCLUSION:
Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3ß/ß-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Diferenciação Celular
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Beta Catenina
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Glicogênio Sintase Quinase 3 beta
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Leucina
Limite:
Animals
Idioma:
En
Revista:
J Sci Food Agric
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China