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Heparanase expression during normal liver development and following partial hepatectomy.
Orit Goldshmidt1, Rita Yeikilis, Nidal Mawasi
1Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel.
The Journal of Pathology
|April 20, 2004
Summary
Heparanase, an enzyme cleaving heparan sulphate, is expressed during liver development and regeneration after partial hepatectomy. Its levels also rise in early liver fibrosis, suggesting a role in liver remodelling.
Area of Science:
- Biochemistry
- Cell Biology
- Hepatology
Background:
- Heparan sulphate proteoglycans are key components of the liver extracellular matrix.
- Heparanase (endo-beta-glucuronidase) cleaves heparan sulphate, potentially influencing liver processes.
- Understanding heparanase's role is crucial for liver development and pathology.
Purpose of the Study:
- To investigate the expression and role of heparanase in liver development, regeneration, and fibrosis.
- To compare heparanase expression with matrix metalloproteinases (MMPs) during these processes.
Main Methods:
- Analysis of heparanase mRNA and protein expression using immunostaining, western blotting, and real-time RT-PCR.
- Assessment of MMP-2 and MMP-9 levels in regenerating and fibrotic liver models.
- Induction of liver fibrosis using thioacetamide.
Main Results:
- Heparanase was expressed during liver development but absent in mature healthy livers.
- Partial hepatectomy induced a biphasic increase in heparanase expression, peaking at 12h and 96-168h post-surgery.
- Elevated heparanase levels were observed in early liver fibrosis, while MMP-2 and MMP-9 increased with fibrosis severity.
Conclusions:
- Heparanase plays a significant role in liver development and tissue remodelling.
- The expression patterns suggest distinct roles for heparanase and MMPs in liver regeneration and fibrosis.