The glomerular basement membrane (GBM) is a kind of net that remains in a state of dynamic equilibrium. Heparan sulfate proteoglycans (HSPGs) are among its most important components. There are much data indicating the significance of these proteoglycans in protecting proteins such as albumins from penetrating to the urine, although some new data indicate that loss of proteoglycans does not always lead to proteinuria. Heparanase is an enzyme which cleaves beta 1,4 D: -glucuronic bonds in sugar groups of HSPGs. Thus it is supposed that heparanase may have an important role in the pathogenesis of proteinuria. Increased heparanase expression and activity in the course of many glomerular diseases was observed. The most widely documented is the significance of heparanase in the pathogenesis of diabetic nephropathy. Moreover, heparanase acts as a signaling molecule and may influence the concentrations of active growth factors in the GBM. It is being investigated whether heparanase inhibition may cause decreased proteinuria. The heparanase inhibitor PI-88 (phosphomannopentaose sulfate) was effective as an antiproteinuric drug in an experimental model of membranous nephropathy. Nevertheless, this drug is burdened by some toxicity, so further investigations should be considered.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00005-009-0061-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fasting mimicking diet in diabetic mice partially preserves glomerular endothelial glycocalyx coverage, without changing the diabetic metabolic environment.
Am J Physiol Renal Physiol
May 2024
Einthoven Laboratory of Vascular and Regenerative Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Intermittent fasting has become of interest for its possible metabolic benefits and reduction of inflammation and oxidative damage, all of which play a role in the pathophysiology of diabetic nephropathy. We tested in a streptozotocin (60 mg/kg)-induced diabetic apolipoprotein E knockout mouse model whether repeated fasting mimicking diet (FMD) prevents glomerular damage. Diabetic mice received 5 FMD cycles in 10 wk, and during cycles 1 and 5 caloric measurements were performed.
View Article and Find Full Text PDFGlycosaminoglycans and fucoidan have a protective effect on experimental glomerulonephritis.
Front Mol Biosci
July 2023
Department of Nephrology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
The glomerular endothelial glycocalyx is degraded during inflammation. The glycocalyx plays a pivotal role in endothelial function and is involved in many processes including binding of chemokines and cytokines, leukocyte trafficking, and preventing proteinuria. HS-based therapeutics are a promising novel class of anti-inflammatory drugs to restore a compromised endothelial glycocalyx under inflammatory conditions.
View Article and Find Full Text PDFHeparanase-2 protein and peptides have a protective effect on experimental glomerulonephritis and diabetic nephropathy.
Front Pharmacol
April 2023
Department of Nephrology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
The endothelial glycocalyx degrading enzyme heparanase-1 (HPSE1) is a major contributor to kidney diseases, such as glomerulonephritis and diabetic nephropathy. Therefore, inhibition of HPSE1 could be an interesting therapeutic strategy to treat glomerular diseases. A possible HPSE1 inhibitor is heparanase-2 (HPSE2) because HPSE2 is a structural homolog of HPSE1 without enzymatic activity.
View Article and Find Full Text PDFPeroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria.
EBioMedicine
April 2023
Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:
Background: Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor ɣ (PPARɣ) agonists can ameliorate proteinuria. Since a recent study showed that PPARɣ regulates HPSE expression in liver cancer cells, we hypothesized that PPARɣ agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.
View Article and Find Full Text PDFEthnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study.
BMJ Open Diabetes Res Care
December 2022
Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Introduction: We aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM).
Research Design And Methods: We included 55 Dutch, 127 South-Asian Surinamese, 92 African Surinamese, 62 Ghanaian, 74 Turkish and 88 Moroccan origin participants with T2DM from the HEalthy LIfe in an Urban Setting study. Using linear regression analyses, we investigated differences in urinary monocyte chemoattractant protein-1 (MCP-1) and heparanase-1 (HPSE-1) levels across ethnic minorities compared with Dutch.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!