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Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria.
Celie, J W A M; Reijmers, R M; Slot, E M; Beelen, R H J; Spaargaren, M; Ter Wee, P M; Florquin, S; van den Born, J.
Affiliation
  • Celie JW; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. p.celie@vumc.nl
Am J Physiol Renal Physiol ; 294(1): F253-63, 2008 Jan.
Article in En | MEDLINE | ID: mdl-18032547
Heparan sulfate proteoglycans (HSPGs) are well known for their proposed role in glomerular filtration. In addition, HSPGs can bind the leukocyte adhesion molecule l-selectin and chemokines, suggesting a role in inflammation. We examined a panel of biopsies representing different human primary kidney diseases for l-selectin and monocyte chemoattractant protein-1 (MCP-1) binding. In various renal diseases, l-selectin and MCP-1 binding to interstitial perivascular matrix HSPGs is increased, which is significantly associated with leukocyte influx. In proteinuric diseases, including membranous glomerulopathy, minimal change disease, but also IgA nephropathy and lupus nephritis, increased binding of l-selectin and MCP-1 to tubular epithelial cell (TEC) HSPGs is observed, which colocalizes with increased basolateral syndecan-1 and anti-heparan sulfate 10E4 staining. Short-hairpin RNA-mediated silencing demonstrates that syndecan-1 on TECs indeed mediates l-Selectin binding. Increased TEC expression of IL-8 in biopsies of proteinuric patients suggests that the increase in luminal protein may activate TECs to increase expression of l-selectin and MCP-1 binding syndecan-1. Strikingly, urinary syndecan-1 from proteinuric patients is less capable of binding l-selectin compared with urinary syndecan-1 from healthy controls, although syndecan-1 concentrations are similar in both groups. Together, our data show pronounced tubulointerstitial HSPG alterations in primary kidney disease, which may affect the inflammatory response.
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Database: MEDLINE Main subject: Proteinuria / Cell Movement / Heparan Sulfate Proteoglycans / Kidney Diseases / Kidney Tubules / Leukocytes Type of study: Observational_studies / Risk_factors_studies Limits: Humans Language: En Journal: Am J Physiol Renal Physiol Journal subject: FISIOLOGIA / NEFROLOGIA Year: 2008 Type: Article Affiliation country: Netherlands
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Database: MEDLINE Main subject: Proteinuria / Cell Movement / Heparan Sulfate Proteoglycans / Kidney Diseases / Kidney Tubules / Leukocytes Type of study: Observational_studies / Risk_factors_studies Limits: Humans Language: En Journal: Am J Physiol Renal Physiol Journal subject: FISIOLOGIA / NEFROLOGIA Year: 2008 Type: Article Affiliation country: Netherlands