Differential Expression of Proteoglycans in Tissue Remodeling and Lymphangiogenesis after Experimental Renal Transplantation in Rats

Heleen Rienstra*, Kirankumar Katta, Johanna W. A. M. Celie, Harry van Goor, Gerjan Navis, Jacob van den Born, Jan-Luuk Hillebrands

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)
312 Downloads (Pure)

Abstract

Background: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction.

Methods: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean) after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin) and chondroitin sulfate proteoglycan (versican) expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively) expression were (semi-) quantitatively analyzed using immunofluorescence.

Findings: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso-and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p

Interpretation: Our results reveal that changes in the extent of expression and the type of proteoglycans being expressed are tightly associated with tissue remodeling after renal transplantation. Therefore, proteoglycans might be potential targets for clinical intervention in renal chronic transplant dysfunction.

Original languageEnglish
Article number9095
Number of pages13
JournalPLoS ONE
Volume5
Issue number2
DOIs
Publication statusPublished - 5-Feb-2010

Keywords

  • HEPARAN-SULFATE PROTEOGLYCANS
  • MUSCLE-CELL PROLIFERATION
  • MONOCYTE CHEMOATTRACTANT PROTEIN-1
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • GLOMERULAR EXTRACELLULAR-MATRIX
  • INTERTUBULAR CAPILLARY CHANGES
  • BASEMENT-MEMBRANE
  • L-SELECTIN
  • LYMPHATIC NEOANGIOGENESIS
  • DIABETIC-NEPHROPATHY

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