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Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model
Xiaowen Cheng1, Juan Jia1, Tianji Zhang2
1SciLifeLab Uppsala, The Biomedical Center, Department of Medical Biochemistry and Microbiology, University of Uppsala, 75237 Uppsala, Sweden.
Cells
|July 9, 2022
Summary
Heparanase exacerbates liver fibrosis by increasing inflammation and cell death. Overexpression of heparanase in mice led to severe, persistent liver damage after carbon tetrachloride exposure.
Area of Science:
- Biochemistry
- Pathology
- Molecular Biology
Background:
- Heparanase (HPSE) is an enzyme implicated in cancer and inflammation.
- Its role in liver fibrosis remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of heparanase in carbon tetrachloride (CCl4)-induced liver fibrosis.
- To compare the fibrotic response in wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice.
Main Methods:
- Induction of liver fibrosis using carbon tetrachloride (CCl4) in WT and Hpa-tg mice.
- Histological analysis to assess tissue damage, fibrosis, and cellular infiltration.
- Evaluation of markers for liver injury, inflammation, and stellate cell activation.
Main Results:
- Hpa-tg mice exhibited significantly more severe liver damage and fibrosis compared to WT mice.
- Heparanase overexpression intensified necrotic tendencies and alpha-smooth muscle actin expression.
- While WT liver damage showed signs of recovery, Hpa-tg liver damage was persistent.
- Increased autophagic activity, apoptosis, and necrosis were observed in Hpa-tg livers.
- A higher number of stellate cells and lipid droplets were noted in Hpa-tg livers.
Conclusions:
- Heparanase significantly exacerbates liver fibrosis and inflammation.
- Heparanase activity contributes to persistent liver damage and hinders recovery.
- Heparanase may represent a therapeutic target for treating liver fibrosis.
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