An in vitro study of zinc-alpha-2-glycoprotein inhibits activation and proliferation of hepatic stellate cells
10.3760/cma.j.issn.1007-3418.2020.02.007
- VernacularTitle:锌α2糖蛋白抑制肝星状细胞活化和增殖的体外研究
- Author:
Shengzheng LUO
1
;
Juncheng WU
;
Renkun LIN
;
Ting LIU
;
Xin LUO
;
Mingyi XU
;
Chuanyong GUO
Author Information
1. 南京医科大学附属上海十院临床医学院消化内科
- Keywords:
Liver cirrhosis;
Hepatic stellate cells;
Zinc-α2-glycoprotein 1
- From:
Chinese Journal of Hepatology
2020;28(2):135-140
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of occurrence and development of zinc-alpha-2-glycoprotein (AZGP1) in the activated hepatic stellate cells (HSCs) and liver fibrosis.Methods The activated human hepatic stellate cell line LX2 was induced by the stimulation of transforming growth factor-β1 to construct carbon tetrachloride liver fibrosis mice model.The situation expression of AZGP1 in liver cells and tissues were observed.Plasmid transfection method was used to detect the activation,proliferation,apoptotic functions and changes in related factors of LX2 cells,respectively,after the overexpression and inhibition of AZGP1expression.Univariate analysis of variance was used for multiple group comparison.Results The results of immunofluorescence staining showed that AZGP1 protein was decreased and α-smooth muscle actin was increased in the activated LX2 cells,and the two were negatively correlated.AZGP1 gene and protein were significantly under-expressed in activated LX2 cells and liver tissues of mice with carbon tetrachloride liver fibrosis.Collagen I,matrix metalloproteinase-2,and α-smooth muscle actin genes and proteins were significantly down-regulated in LX2 cells after over-expression of AZGP 1.Cell fluorescence showed that AZGP 1-overexpressing cells were activated and α-smooth muscle actin protein was reduced.In addition,the proliferative activity and G1/S-specific cyclin D1 protein of LX2 cells were significantly reduced after overexpression of AZGP1,while cell cycle experiments showed that the proportion of cells overexpressing AZGP1 was significantly increased in the G0/G1 phase,and the proportion of S phase was significantly reduced.AZGP1 had no significant effect on the apoptosis of LX2 cells.Conclusion AZGP1 can reverse liver fibrosis by inhibiting the activation and proliferation of hepatic stellate cells,and thereby overexpression of AZGP1 is expected to become a new target for liver fibrosis treatment.
