PMID- 18032547
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20110428
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 294
IP  - 1
DP  - 2008 Jan
TI  - Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases 
      correlate with leukocyte influx and proteinuria.
PG  - F253-63
AB  - 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.
FAU - Celie, J W A M
AU  - Celie JW
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands. p.celie@vumc.nl
FAU - Reijmers, R M
AU  - Reijmers RM
FAU - Slot, E M
AU  - Slot EM
FAU - Beelen, R H J
AU  - Beelen RH
FAU - Spaargaren, M
AU  - Spaargaren M
FAU - Ter Wee, P M
AU  - Ter Wee PM
FAU - Florquin, S
AU  - Florquin S
FAU - van den Born, J
AU  - van den Born J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071121
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Heparan Sulfate Proteoglycans)
RN  - 0 (SDC1 protein, human)
RN  - 0 (Syndecan-1)
RN  - 126880-86-2 (L-Selectin)
SB  - IM
MH  - Biopsy
MH  - Case-Control Studies
MH  - Cell Line
MH  - Cell Movement/*physiology
MH  - Chemokine CCL2/metabolism
MH  - Disease Progression
MH  - Epithelial Cells/metabolism/pathology
MH  - Heparan Sulfate Proteoglycans/*metabolism
MH  - Humans
MH  - Kidney Diseases/*metabolism/pathology
MH  - Kidney Tubules/*metabolism/pathology
MH  - L-Selectin/metabolism
MH  - Leukocytes/*pathology
MH  - Proteinuria/*metabolism/pathology
MH  - Syndecan-1/urine
EDAT- 2007/11/23 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/11/23 09:00
PHST- 2007/11/23 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/11/23 09:00 [entrez]
AID - 00429.2007 [pii]
AID - 10.1152/ajprenal.00429.2007 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2008 Jan;294(1):F253-63. doi: 
      10.1152/ajprenal.00429.2007. Epub 2007 Nov 21.