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Cited by 89Renal Diseases and GlomerulopathiesProteoglycans and glycosaminoglycans researchVasculitis and related conditions

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Heparanase Is Involved in the Pathogenesis of Proteinuria as a Result of Glomerulonephritis

Levidiotis, Vicki, Freeman, Craig, Tikellis, Chris, Cooper, Mark E., Power, David A.·2004·Journal of the American Society of Nephrology
DOI 10.1097/01.asn.0000103229.25389.40
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Abstract

The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of heparan sulfate proteoglycans within the glomerular basement membrane. A loss of negatively charged heparan sulfate proteoglycans may result in alteration of the permselective properties of the glomerular basement membrane, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. In this study, therefore, the role of heparanase in passive Heymann nephritis (PHN) was examined. Normal glomeruli showed low-level heparanase expression as determined by immunohistochemistry and Western blot analysis. Days 5, 14, and 28 of PHN were associated with an increase in endothelial and glomerular epithelial cell heparanase. Reverse transcription-PCR confirmed a significant increase in mRNA at day 21 of disease (P < 0.0004). Furthermore, urinary and glomerular heparanase activities were significantly increased at days 5 and 21 of disease, respectively. Western blot analysis of isolated glomeruli separated into membrane- and cytosol-enriched protein fractions showed that the active 58-kD heparanase species was increased but restricted to the cytosol of diseased glomeruli at day 21. The inactive 65-kD precursor, however, was found in membrane and cytosol-diseased fractions, suggesting cell membrane processing. Complement depletion prevented glomerular heparanase expression; in addition, administration of a polyclonal anti-heparanase antibody significantly reduced urinary protein excretion at day 5 of disease to 62 +/- 11 mg/d compared with 203 +/- 43 and 159 +/- 18 mg/d in the normal rabbit serum- and normal saline-treated experimental groups, respectively (P < 0.002). Proteinuria was reduced in the absence of any altered glomerular C5b-9 activity, sheep IgG deposition, or rat anti-sheep antibody titers. These data suggest that heparanase contributes to the pathogenesis of proteinuria in PHN.

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Crossref · 10.1097/01.asn.0000103229.25389.40

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Metadata

Authors
Levidiotis, V., Freeman, C., Tikellis, C., Cooper, M. E., & Power, D. A.
Affiliations
  • The University of Melbourne (AU)
  • Australian National University (AU)
  • Baker Heart and Diabetes Institute (AU)
  • Austin Health (AU)
ORCID
Venue
Journal of the American Society of Nephrology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-01
Volume
15
Issue
1
Pages
68-78
ISSN
1046-6673 (ISSN-L)
DOI
10.1097/01.asn.0000103229.25389.40
OpenAlex
W2137907593
Cited by
89
References
48
Citations by year
2025: 4 · 2024: 1 · 2023: 3 · 2022: 6 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 6 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 2
FWCI
6.61
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of the American Society of Nephrology (publishedVersion)
  • PubMed (publishedVersion)
  • ANU Open Research (Australian National University) (submittedVersion)
Funders
  • American Society of Nephrology
  • Amgen
  • Kidney Health Australia
  • National Health and Medical Research Council
  • National Medical Research Council
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Rheumatology › Vasculitis and related conditions
Keywords
heparanase, proteinuria, passive Heymann nephritis, glomerulonephritis, heparan sulfate proteoglycans, glomerular basement membrane, glomerular permeability, complement depletion, glomerular endothelial cells, glomerular epithelial cells
MeSH terms
Heparanase, Animals, Antibodies, Glomerulonephritis, Glucuronidase, Proteinuria, Rabbits

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