Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-ß production.
Mol Metab
; 78: 101828, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-37898449
ABSTRACT
OBJECTIVE:
FAS-mediated apoptosis of hepatocytes and aberrant TGF-ß signaling are major drivers of liver fibrosis. Decreased miRNA let-7 expression in the livers of patients and animals with fibrosis suggests a mechanistic link of let-7 to hepatic fibrogenesis.METHODS:
Using transient transfection we tested the effects of let-7 overexpression and TET3 siRNA knockdown on FAS and TGF-ß1 expression and FAS-mediated apoptosis in human and mouse primary hepatocytes. We assessed the therapeutic activity of let-7 miRNA delivered via adeno-associated viral vectors in mouse models of carbon tetrachloride (CCl4)-induced and bile duct ligation (BDL)-induced liver fibrosis.RESULTS:
Let-7 decreased TGF-ß1 production from hepatocytes through a negative feedback loop involving TET3. On the other hand, let-7 post-transcriptionally inhibits FAS expression, thereby suppressing hepatocyte apoptosis. Hepatic-specific delivery of let-7 miRNA mitigated liver fibrosis in both CCl4 and BDL mouse models.CONCLUSIONS:
Let-7 is a crucial node in the signaling networks that govern liver fibrosis progression. Let-7 and/or its derivatives may be used as therapeutic agents for liver fibrosis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Factor de Crecimiento Transformador beta1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Metab
Año:
2023
Tipo del documento:
Article
País de afiliación:
China