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  • Garsen, MarjoleinRadboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands. (author)

Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • Elsevier BV,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-294680
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-294680URI
  • https://doi.org/10.1016/j.ajpath.2015.12.008DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Benner, MarilenRadboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands. (author)
  • Dijkman, Henry B.Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 GA Nijmegen, Netherlands. (author)
  • van Kuppevelt, Toin H.Radboud Univ Nijmegen, Med Ctr, Dept Biochem, NL-6525 GA Nijmegen, Netherlands. (author)
  • Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)jinpili (author)
  • RabeLink, Ton J.Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands. (author)
  • Vlodavsky, IsraelTechnion Israel Inst Technol, Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, POB 9649, IL-31096 Haifa, Israel. (author)
  • Berden, Jo H. M.Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands. (author)
  • Rops, Angeligue L. W. M. M.Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands. (author)
  • Elkin, MichaelHadassah Hebrew Univ, Med Ctr, Sharett Inst, Jerusalem, Israel. (author)
  • van der Vlag, JohanRadboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands. (author)
  • Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 GA Nijmegen, Netherlands.Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 GA Nijmegen, Netherlands. (creator_code:org_t)

Related titles

  • In:American Journal of Pathology: Elsevier BV186:4, s. 805-8150002-94401525-2191

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