Dynamic change of hepatocyte during PXR-induced liver enlargement
10.16438/j.0513-4870.2021-0493
- VernacularTitle:PXR所致小鼠肝增大的肝细胞动态变化研究
- Author:
Jia-ning TIAN
;
Rui-min WANG
;
Xiao YANG
;
Jie YANG
;
Yi-fei ZHANG
;
Min HUANG
;
Hui-chang BI
- Publication Type:Research Article
- Keywords:
pregnane X receptor;
liver enlargement;
hepatocyte enlargement;
hepatocyte proliferation
- From:
Acta Pharmaceutica Sinica
2021;56(5):1360-1368
- CountryChina
- Language:Chinese
-
Abstract:
Pregnane X receptor (PXR), a member of nuclear receptor superfamily, plays an important role in xenobiotic and endogenous metabolism, endocrine balance, and cell proliferation, etc. Previous study has shown that pregnenolone 16α-carbonitrile (PCN), a mouse PXR agonist, could induce liver enlargement. And we found that the change in hepatocytes exhibits regional distribution characteristics: hepatocyte enlargement occurs around the central vein (CV) area, while hepatocyte proliferation occurs around the portal vein (PV) area. In this study, the dynamic changes of hepatocytes during PXR-induced liver enlargement were determined. Serum and liver samples from male C57BL/6 mice were collected for biochemical and pathological analysis after PCN treatment for 1, 2, 3, 5 days, respectively. The animal experiment was approved by the Animal Ethics Committee of Sun Yat-Sen University. The results showed that with the increase in the PCN treatment days, the feature of this regional change of hepatocyte around the CV and PV areas became more and more obvious. At the same time, the factors related to hepatocyte enlargement, such as the expression of PXR downstream genes and the hepatic content of triglyceride (TG), has gradually increased. The upregulation of proliferation-related proteins and downregulation of cyclin-dependent kinases inhibitor proteins were observed in the early stage of PCN treatment, suggesting that hepatocyte proliferation occurs earlier than hepatocyte enlargement during PXR-induced liver enlargement. This study reveals the dynamic change of hepatocytes during PXR-induced liver enlargement and provides a new insight in liver enlargement promoted via PXR activation.
