Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9679
Full metadata record
DC FieldValueLanguage
dc.contributor.authorLevidiotis, Vickien
dc.contributor.authorFreeman, Craigen
dc.contributor.authorTikellis, Christosen
dc.contributor.authorCooper, Mark Een
dc.contributor.authorPower, David Anthonyen
dc.date.accessioned2015-05-15T22:51:45Z
dc.date.available2015-05-15T22:51:45Z
dc.date.issued2004-01-01en
dc.identifier.citationJournal of the American Society of Nephrology : Jasn; 15(1): 68-78en
dc.identifier.govdoc14694159en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9679en
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherAntibodies.analysisen
dc.subject.otherGlomerulonephritis.complications.enzymology.pathologyen
dc.subject.otherGlucuronidase.biosynthesis.immunology.metabolism.physiologyen
dc.subject.otherProteinuria.etiologyen
dc.subject.otherRabbitsen
dc.titleHeparanase is involved in the pathogenesis of proteinuria as a result of glomerulonephritis.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of the American Society of Nephrology : JASNen
dc.identifier.affiliationDepartment of Nephrology, Austin Research Institute, and Department of Medicine, University of Melbourne, Austin & Repatriation Medical Center, Studley Road, Heidelberg, Victoria, Australiaen
dc.description.pages68-78en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/14694159en
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.cerifentitytypePublications-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

8
checked on Feb 7, 2023

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.