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Published on: August 19, 2020
Heparanase in glomerular diseases.
M J van den Hoven1, A L Rops, I Vlodavsky
1Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences and Division of Nephrology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Heparanase enzyme activity contributes to proteinuric diseases by degrading heparan sulfate in the glomerular basement membrane. Inhibitors of heparanase may offer a novel therapeutic strategy for these conditions.
Area of Science:
- Nephrology
- Biochemistry
- Molecular Biology
Background:
- Heparanase (HPSE) is an enzyme that degrades heparan sulfate (HS) polysaccharides.
- Established roles in metastasis, angiogenesis, and inflammation.
- Emerging evidence links HPSE to proteinuric diseases.
Purpose of the Study:
- Review the role of HPSE in HS degradation within proteinuric diseases.
- Discuss potential therapeutic strategies targeting HPSE.
Main Methods:
- Literature review of studies on HPSE and proteinuric diseases.
- Analysis of proposed mechanisms of HPSE-induced proteinuria.
- Evaluation of heparin(oids) as potential HPSE inhibitors.
Main Results:
- Increased glomerular HPSE expression correlates with HS loss in the glomerular basement membrane (GBM) and proteinuria.
- Elevated HPSE activity detected in urine of proteinuric patients.
- Transgenic mice overexpressing HPSE exhibit mild proteinuria.
Conclusions:
- HPSE activity in glomeruli may cause HS loss, leading to proteinuria through various mechanisms including altered cell-GBM interactions, factor release, or intracellular signaling.
- Further research is needed to elucidate the prevailing mechanism and triggers for increased HPSE expression.
- HPSE inhibitors, like heparin(oids), represent a potential therapeutic avenue for proteinuric diseases.
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