title: Incipient renal transplant dysfunction associates with tubular syndecan-1 expression and shedding.
abstract: Syndecan-1 is a transmembrane heparan sulfate proteoglycan involved in regenerative growth and cellular adhesion. We hypothesized that the induction of tubular syndecan-1 is a repair response to incipient renal damage in apparently stable, uncomplicated renal transplant recipients. We quantified tubular syndecan-1 in unselected renal protocol biopsies taken 1 yr after transplantation. Spearman rank correlation analysis revealed an inverse correlation between tubular syndecan-1 expression and creatinine clearance at the time of biopsy (r = -0.483, P < 0.03). In a larger panel of protocol and indication biopsies from renal transplant recipients, tubular syndecan-1 correlated with tubular proliferation marker Ki67 (r = 0.518, P < 0.0001). In a rat renal transplantation model, 2 mo after transplantation, mRNA expression of syndecan-1 and its major sheddase, A disintegrin and metalloproteinase-17, were upregulated (both P < 0.03). Since shed syndecan-1 might end up in the circulation, in a stable cross-sectional human renal transplant population (n = 510), we measured plasma syndecan-1. By multivariate regression analysis, we showed robust independent associations of plasma syndecan-1 with renal (plasma creatinine and plasma urea) and endothelial function parameters (plasma VEGF-A, all P < 0.01). By various approaches, we were not able to localize syndecan-1 in vessel wall or endothelial cells, which makes shedding of syndecan-1 from the endothelial glycocalyx unlikely. Our data suggest that early damage in transplanted kidneys induces repair mechanisms within the graft, namely, tubular syndecan-1 expression for tubular regeneration and VEGF production for endothelial repair. Elevated plasma syndecan-1 levels in renal transplantation patients might be interpreted as repair/survival factor related to loss of tubular and endothelial function in transplanted kidneys.
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Saritha
authors.initials: S
authors.lastname: Adepu
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Colin W K
authors.initials: CW
authors.lastname: Rosman
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Wendy
authors.initials: W
authors.lastname: Dam
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Nephrology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands; and j.van.den.born@umcg.nl.
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011920:Rats, Inbred WF; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism*; D053668:Syndecan-1 / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D053668:Syndecan-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; D000072198:ADAM17 Protein
keywords: kidney function; renal biopsies; renal transplantation; syndecan-1; vascular endothelial growth factor