title: Expression of sialidase and dystroglycan in human glomerular diseases.
abstract: BACKGROUND
  alpha-Dystroglycan (alpha-DG) is a negatively charged glycoprotein that covers the surface of podocytes. A decreased glomerular expression of alpha-DG has been described in minimal change nephropathy (MCN), but not in focal segmental glomerulosclerosis (FSGS). This was suggested as a tool to distinguish these diseases. Sialic acid is a negatively charged carbohydrate extensively present on both alpha-DG and podocalyxin, which is also expressed on podocytes. Intrarenal perfusion with bacterial sialidase leads to foot process effacement and proteinuria. This is the first study on the expression of endogenous glomerular sialidase; furthermore, the expression of dystroglycan was re-evaluated.
  
  
  METHODS
  The expression of alpha-DG and sialidase was investigated by immunofluorescence in kidney biopsies of patients with MCN (n = 5), FSGS (n = 15), proliferative lupus nephritis (LN, n = 9), membranous glomerulopathy (MG, n = 10) and normal human kidneys (NHK, n = 4). The urinary sialic acid concentration was measured using a newly developed LC-tandem mass spectrometry method.
  
  
  RESULTS
  A 3-fold increased glomerular expression of sialidase was found in MG, accompanied with an increased urinary sialic acid concentration in two MG patients. However, we did not observe major changes in the expression of alpha-DG in patients with the above-mentioned glomerular diseases compared to NHK, also not between MCN and FSGS.
  
  
  CONCLUSIONS
  Endogenous glomerular sialidase expression is increased in MG, which might represent a novel mechanism for the loss of negative charge in the glomerular capillary filter. The expression of dystroglycan cannot be used as a diagnostic tool to differentiate between glomerular diseases.
authors.affiliation: Department of Nephrology, Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Nils P J
authors.initials: NP
authors.lastname: Vogtländer
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Marinka A H
authors.initials: MA
authors.lastname: Bakker
authors.forename: Henry B
authors.initials: HB
authors.lastname: Dijkman
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D049030:Dystroglycans / Q000096:biosynthesis*; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D006801:Humans; D008181:Lupus Nephritis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000378:metabolism*; D009439:Neuraminidase / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D049030:Dystroglycans; D009439:Neuraminidase