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.
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: Kristina M Niculovic; Linda Blume; Henri Wedekind; Elina Kats; Iris Albers; Stephanie Groos; Markus Abeln; Jessica Schmitz; Esther Beuke; Jan H Bräsen; Anette Melk; Mario Schiffer; Birgit Weinhold; Anja K Münster-Kühnel Journal: J Am Soc Nephrol Date: 2019-04-30 Impact factor: 10.121
Authors: Sravan Kakani; Tal Yardeni; Justin Poling; Carla Ciccone; Terren Niethamer; Enriko D Klootwijk; Irini Manoli; Daniel Darvish; Shelley Hoogstraten-Miller; Patricia Zerfas; E Tian; Kelly G Ten Hagen; Jeffrey B Kopp; William A Gahl; Marjan Huizing Journal: Am J Pathol Date: 2012-02-07 Impact factor: 4.307
Authors: Bart Smeets; Fabien Stucker; Jack Wetzels; Isabelle Brocheriou; Pierre Ronco; Hermann-Josef Gröne; Vivette D'Agati; Agnes B Fogo; Toin H van Kuppevelt; Hans-Peter Fischer; Peter Boor; Jürgen Floege; Tammo Ostendorf; Marcus J Moeller Journal: Am J Pathol Date: 2014-10-07 Impact factor: 4.307
Authors: María José Hernández-Corbacho; Russell W Jenkins; Christopher J Clarke; Yusuf A Hannun; Lina M Obeid; Ashley J Snider; Leah J Siskind Journal: PLoS One Date: 2011-06-08 Impact factor: 3.240