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Reduction of anionic sites in the glomerular basement membrane by heparanase does not lead to proteinuria
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2008 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 73, no 3, 278-287 p.Article in journal (Refereed) Published
Abstract [en]

Heparan sulfate in the glomerular basement membrane has been considered crucial for charge-selective filtration. In many proteinuric diseases, increased glomerular expression of heparanase is associated with decreased heparan sulfate. Here, we used mice overexpressing heparanase and evaluated the expression of different heparan sulfate domains in the kidney and other tissues measured with anti-heparan sulfate antibodies. Glycosaminoglycan-associated anionic sites were visualized by the cationic dye cupromeronic blue. Transgenic mice showed a differential loss of heparan sulfate domains in several tissues. An unmodified and a sulfated heparan sulfate domain resisted heparanase action in vivo and in vitro. Glycosaminoglycan-associated anionic sites were reduced about fivefold in the glomerular basement membrane of transgenic mice, whereas glomerular ultrastructure and renal function remained normal. Heparanase-resistant heparan sulfate domains may represent remnant chains or chains not susceptible to cleavage. Importantly, the strong reduction of glycosaminoglycan-associated anionic sites in the glomerular basement membrane without development of a clear renal phenotype questions the primary role of heparan sulfate in charge-selective filtration. We cannot, however, exclude that overexpression of heparanase and heparan sulfate loss in the basement membrane in glomerular diseases contributes to proteinuria.

Place, publisher, year, edition, pages
2008. Vol. 73, no 3, 278-287 p.
Keyword [en]
transgenic mouse, glomerular filtration barrier, renal function
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-99788DOI: 10.1038/sj.ki.5002706ISI: 000252388300007PubMedID: 18046314OAI: oai:DiVA.org:uu-99788DiVA: diva2:208742
Available from: 2009-03-19 Created: 2009-03-19 Last updated: 2011-06-28Bibliographically approved

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Li, Jin-Ping
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