Fulltext:
172662.pdf
Embargo:
until further notice
Size:
1.289Mb
Format:
PDF
Description:
Publisher’s version
Publication year
2016Source
American Journal of Pathology, 186, 4, (2016), pp. 805-15ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Nephrology
Pathology
Biochemistry (UMC)
Journal title
American Journal of Pathology
Volume
vol. 186
Issue
iss. 4
Page start
p. 805
Page end
p. 15
Subject
Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238430]
- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.