Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration.
Cell Commun Signal
; 22(1): 95, 2024 02 02.
Article
em En
| MEDLINE
| ID: mdl-38308318
ABSTRACT
BACKGROUND:
The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration.METHODS:
The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1).RESULTS:
Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly.CONCLUSION:
Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Commun Signal
Ano de publicação:
2024
Tipo de documento:
Article