Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria

Autor: Marcel Spaargaren, P.M. (Piet) ter Wee, Robert H.J. Beelen, Johanna W.A.M. Celie, Rogier M. Reijmers, Edith M. Slot, Sandrine Florquin, J. van den Born
Přispěvatelé: Pathology, CCA -Cancer Center Amsterdam, AII - Amsterdam institute for Infection and Immunity, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Molecular cell biology and Immunology, Nephrology, IOO, CCA - Immuno-pathogenesis, ICaR - Ischemia and repair
Rok vydání: 2008
Předmět:
Zdroj: 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 2008, ' Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria ', American Journal of Physiology.Renal, Fluid and Electrolyte Physiology, vol. 294, no. 1, pp. F253-F263 . https://doi.org/10.1152/ajprenal.00429.2007
American journal of physiology. Renal physiology, 294(1), F253-F263. American Physiological Society
American journal of physiology-Renal physiology, 294(1), F253-F263. AMER PHYSIOLOGICAL SOC
American Journal of Physiology.Renal, Fluid and Electrolyte Physiology, 294(1), F253-F263. American Physiological Society
ISSN: 0363-6127
1931-857X
DOI: 10.1152/ajprenal.00429.2007
Popis: 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.
Databáze: OpenAIRE