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Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis
Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands..
Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands..
Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 GA Nijmegen, Netherlands..
Radboud Univ Nijmegen, Med Ctr, Dept Biochem, NL-6525 GA Nijmegen, Netherlands..
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2016 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 186, no 4, 805-815 p.Article in journal (Refereed) PublishedText
Abstract [en]

Heparanase, a heparan sulfate (HS)-specific endoglucuronidase, mediates the onset of proteinuria and renal damage during experimental diabetic nephropathy. Glomerular heparanase expression is increased in most proteinuric diseases. Herein, we evaluated the role of heparanase in two models of experimental glomerulonephritis, being anti-glomerular basement membrane and lipopolysaccharide-induced glomerulonephritis, in wild-type and heparanase-deficient mice. Induction of experimental glomerulonephritis Led to an increased heparanase expression in wild-type mice, which was associated with a decreased glomerular expression of a highly sulfated HS domain, and albuminuria. Albuminuria was reduced in the heparanase-deficient mice in both models of experimental glomerulonephritis, which was accompanied by a better renal function and less renal damage. Notably, glomerular HS expression was preserved in the heparanase-deficient mice. Glomerular leukocyte and macrophage influx was reduced in the heparanase-deficient mice, which was accompanied by a reduced expression of both types 1 and 2 helper T-cell cytokines. In vitro, tumor necrosis factor-alpha and Lipopolysaccharide directly induced heparanase expression and increased transendothelial albumin passage. Our study shows that heparanase contributes to proteinuria and renal damage in experimental glomerulonephritis by decreasing glomerular HS expression, enhancing renal leukocyte and macrophage influx, and affecting the Local cytokine milieu.

Place, publisher, year, edition, pages
2016. Vol. 186, no 4, 805-815 p.
National Category
Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-294680DOI: 10.1016/j.ajpath.2015.12.008ISI: 000373413900008PubMedID: 26873445OAI: oai:DiVA.org:uu-294680DiVA: diva2:932258
Available from: 2016-06-01 Created: 2016-05-26 Last updated: 2016-06-01Bibliographically approved

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Li, Jin-Ping
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