title: No change in glomerular heparan sulfate structure in early human and experimental diabetic nephropathy.
abstract: Heparan sulfate (HS) proteoglycans are major anionic glycoconjugates of the glomerular basement membrane and are thought to contribute to the permeability properties of the glomerular capillary wall. In this study we evaluated whether the development of (micro) albuminuria in early human and experimental diabetic nephropathy is related to changes in glomerular HS expression or structure. Using a panel of recently characterized antibodies, glomerular HS expression was studied in kidney biopsies of type I diabetic patients with microalbuminuria or early albuminuria and in rat renal tissue after 5 months diabetes duration. Glomerular staining, however, revealed no differences between control and diabetic specimens. A significant (p < 0.05) approximately 60% increase was found in HS N-deacetylase activity, a key enzyme in HS sulfation reactions, in diabetic glomeruli. Structural analysis of glomerular HS after in vivo and in vitro radiolabeling techniques revealed no changes in HS N-sulfation or charge density. Also HS chain length, protein binding properties, as well as disaccharide composition did not differ between control and diabetic glomerular HS samples. These results indicate that in experimental and early human diabetic nephropathy, increased urinary albumin excretion is not caused by loss of glomerular HS expression or sulfation and suggest other mechanisms to be responsible for increased glomerular albumin permeability.
authors.affiliation: Department of Nephrology, Radboud University Medical Center Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. jvandenborn@vumc.nl
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.forename: Brenda
authors.initials: B
authors.lastname: Pisa
authors.forename: Marinka A H
authors.initials: MA
authors.lastname: Bakker
authors.forename: Johanna W A M
authors.initials: JW
authors.lastname: Celie
authors.forename: Carin
authors.initials: C
authors.lastname: Straatman
authors.forename: Steven
authors.initials: S
authors.lastname: Thomas
authors.forename: Gian C
authors.initials: GC
authors.lastname: Viberti
authors.forename: Lena
authors.initials: L
authors.lastname: Kjellen
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D006497:Heparan Sulfate; D013311:Streptozocin