title: Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation.
abstract: Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control. Increased epithelial syndecan-1 in allografts correlated with low proteinuria and serum creatinine, less interstitial inflammation, less tubular atrophy, and prolonged allograft survival. Knockdown of syndecan-1 in human tubular epithelial cells in vitro reduced cell proliferation. Selective binding of growth factors suggests that syndecan-1 may promote epithelial restoration. Bilateral renal ischemia/reperfusion in syndecan-1-deficient mice resulted in increased initial renal failure and tubular injury compared with wild-type mice. Macrophage and myofibroblast numbers, tubular damage, and plasma urea levels were increased, and tubular proliferation reduced in the kidneys of syndecan-1 deficient compared with wild-type mice 14 days following injury. Hence syndecan-1 promotes tubular survival and repair in murine ischemia/reperfusion injury and correlates with functional improvement in human renal allograft transplantation.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johanna W A M
authors.initials: JW
authors.lastname: Celie
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Katta
authors.forename: Saritha
authors.initials: S
authors.lastname: Adepu
authors.forename: Wynand B W H
authors.initials: WB
authors.lastname: Melenhorst
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Reijmers
authors.forename: Edith M
authors.initials: EM
authors.lastname: Slot
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Marcel
authors.initials: M
authors.lastname: Spaargaren
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Jaap J Homan
authors.initials: JJ
authors.lastname: van der Heide
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000502:physiology*; D007684:Kidney Tubules / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D015427:Reperfusion Injury / Q000503:physiopathology*; D053668:Syndecan-1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1