Notch signaling pathway regulates cell cycle in proliferating hepatocytes involved in liver regeneration.
J Gastroenterol Hepatol
; 33(8): 1538-1547, 2018 Aug.
Article
em En
| MEDLINE
| ID: mdl-29384233
ABSTRACT
BACKGROUND AND AIM:
It has been well documented that Notch signaling is involved in liver regeneration. However, the exact molecular mechanism mediating this process is not fully elucidated. The current study aimed to investigate the role of Notch signaling regulating cell cycle in proliferating hepatocytes in liver regeneration after partial hepatectomy (PHx, 67% resection) and the related molecular mechanism.METHODS:
Partial hepatectomy was performed in Sprague Dawley rats, and remnant livers were harvested 0, 1, 3, 5, and 7 days after operation, and primary hepatocytes were isolated to investigate the molecular mechanism.RESULTS:
Notch signaling activation and hepatocyte proliferation were significantly increased after PHx, while treatment with FLI-06, the inhibitor of γ-secreting enzyme, blocked these trends. Besides, inhibition of Notch signaling led to dysregulation of cell cycle and cell-cycle components. Furthermore, Akti-1/2 (a selective Akt inhibitor) and PX-478 (a selective Hif-1α inhibitor) inhibited hepatocyte proliferation and liver regeneration after PHx, and the effect of downstream molecules activation by Jagged-1 (Notch-1 ligand) in hepatocytes was abolished by FLI-06, Akti-1/2, and PX-478.CONCLUSION:
The current study demonstrated for the first time that Notch signaling regulated cell cycle in proliferating hepatocytes involved in liver regeneration through NICD/Akt Akt/Hif-1α pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Ciclo Celular
/
Hepatócitos
/
Proliferação de Células
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Receptores Notch
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Regeneração Hepática
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China