11ßhydroxysteroid dehydrogenase1 is associated with the activation of hepatic stellate cells in the development of hepatic fibrosis.
Mol Med Rep
; 22(4): 3191-3200, 2020 Oct.
Article
in En
| MEDLINE
| ID: mdl-32945429
ABSTRACT
Hepatic fibrosis (HF) is a common complication of numerous chronic liver diseases, but predominantly results from persistent liver inflammation or injury. If left untreated, HF can progress and develop into liver cirrhosis and even hepatocellular carcinoma. However, the underlying molecular mechanisms of HF remain unknown. The present study aimed to investigate the role of 11ßhydroxysteroid dehydrogenase1 (11ßHSD1) during the development of hepatic fibrosis. An experimental rat model of liver fibrosis was induced using porcine serum. 11ßHSD1 gene expression levels and enzyme activity during hepatic fibrogenesis were assessed. 11ßHSD1 gene knockdown using small interfering RNA and overexpression were performed in LX2human hepatic stellate cells (HSCs). HSCs were stimulated with transforming growth factorß1 (TGFß1). Cell cycle distribution, proliferation, collagen secretion and 11ßHSD1 gene activity in HSCs were compared before and after stimulation. As hepatic fibrosis progressed, 11ßHSD1 gene expression and activity increased, indicating a positive correlation with typical markers of liver fibrosis. 11ßHSD1 inhibition markedly reduced the degree of fibrosis. The cell proliferation was increased, the number of cells in the G0/G1 phase decreased and the number of cells in the S and G2/M phases increased in the pSuper transfected group compared with the N group. In addition, the overexpression of 11ßHSD1 enhanced the TGFß1induced activation of LX2HSCs and enzyme activity of connective tissue growth factor. 11ßHSD1 knockdown suppressed cell proliferation by blocking the G0/G1 phase of the cell cycle, which was associated with HSC stimulation and inhibition of 11ßHSD1 enzyme activity. In conclusion, increased 11ßHSD1 expression in the liver may be partially responsible for hepatic fibrogenesis, which is potentially associated with HSC activation and proliferation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
11-beta-Hydroxysteroid Dehydrogenase Type 1
/
Transforming Growth Factor beta1
/
Hepatic Stellate Cells
/
Liver Cirrhosis, Experimental
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mol Med Rep
Year:
2020
Document type:
Article