Effect of ADHI on hepatic stellate cell activation and liver fibrosis in mice.
Biochem Biophys Res Commun
; 651: 98-106, 2023 04 09.
Article
em En
| MEDLINE
| ID: mdl-36801615
ABSTRACT
The relationship between alcohol dehydrogenase (ADH) and liver fibrosis has been studied, but the mechanism of ADH involvement in liver fibrosis remains unclear. The aim of the present study was to explore the role of ADHI, the classical liver ADH, in hepatic stellate cell (HSC) activation and the effect of 4-methylpyrazole (4-MP), an ADH inhibitor, on liver fibrosis induced by carbon tetrachloride (CCl4) in mice. The results showed that overexpression of ADHI significantly increases proliferation, migration, adhesion and invasion rates of HSC-T6 cells as compared with controls. When HSC-T6 cells were activated by ethanol, TGF-ß1 or LPS, the expression of ADHI was elevated significantly (P < 0.05). Overexpression of ADHI significantly increased the levels of COL1A1 and α-SMA, markers of HSC activation. Moreover, the expression of COL1A1 and α-SMA was decreased significantly by transfection of ADHI siRNA (P < 0.01). In a liver fibrosis mouse model ADH activity increased significantly and was highest in the 3rd week. The activity of ADH in the liver was correlated with its activity in the serum (P < 0.05). 4-MP significantly decreased ADH activity and ameliorated liver injury, and ADH activity was positively correlated with the Ishak score of liver fibrosis. In conclusion, ADHI plays an important role in the activation of HSC, and inhibition of ADH ameliorates liver fibrosis in mice.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Estreladas do Fígado
/
Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article