The role of forkhead box M1-methionine adenosyltransferase 2 A/2B axis in liver inflammation and fibrosis.
Nat Commun
; 15(1): 8388, 2024 Sep 27.
Article
en En
| MEDLINE
| ID: mdl-39333125
ABSTRACT
Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl4) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl4-induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1Hep-/-, hepatocytes from Foxm1HSC-/-, and HSCs and hepatocytes from Foxm1KC-/- have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tetracloruro de Carbono
/
Hepatocitos
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Células Estrelladas Hepáticas
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Proteína Forkhead Box M1
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Macrófagos del Hígado
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Cirrosis Hepática
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Metionina Adenosiltransferasa
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos