Expression of sialidase and dystroglycan in human glomerular diseases

Nils P J Vogtländer1, Johan van der Vlag, Marinka A H Bakker

  • 1Department of Nephrology, Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.

Abstract

Insights

Glomerular sialidase expression increases in membranous glomerulopathy (MG), potentially causing charge loss in kidney filters. Dystroglycan expression does not reliably distinguish between minimal change nephropathy and focal segmental glomerulosclerosis.

Area of Science:

  • Nephrology
  • Glomerular Biology
  • Biochemistry

Background:

  • Alpha-dystroglycan (alpha-DG) is a key podocyte glycoprotein involved in glomerular filtration.
  • Previous studies suggested alpha-DG expression differences could distinguish minimal change nephropathy (MCN) from focal segmental glomerulosclerosis (FSGS).
  • Sialic acid, a component of alpha-DG, contributes to the glomerular filter's negative charge; exogenous sialidase causes podocyte damage.

Purpose of the Study:

  • To investigate endogenous glomerular sialidase expression in various kidney diseases.
  • To re-evaluate dystroglycan expression in these conditions.
  • To explore the role of sialidase in glomerular charge abnormalities.

Main Methods:

  • Immunofluorescence was used to assess glomerular alpha-DG and sialidase expression in kidney biopsies from patients with MCN, FSGS, lupus nephritis (LN), membranous glomerulopathy (MG), and normal kidney controls (NHK).
  • Urinary sialic acid levels were quantified using LC-tandem mass spectrometry.
  • Statistical analysis compared expression levels across disease groups.

Main Results:

  • Glomerular sialidase expression was significantly increased (3-fold) in membranous glomerulopathy (MG) compared to normal kidneys.
  • Elevated urinary sialic acid concentrations were observed in two MG patients.
  • No significant changes in alpha-dystroglycan (alpha-DG) expression were found across the studied glomerular diseases, including between MCN and FSGS.

Conclusions:

  • Increased endogenous glomerular sialidase in MG may contribute to the loss of negative charge in the glomerular filter.
  • Dystroglycan expression is not a reliable biomarker for differentiating between MCN and FSGS.
  • These findings highlight a potential role for sialidase in the pathogenesis of glomerular diseases like MG.

Related Concept Videos

Proteoglycans01:05

Proteoglycans

Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Nephrotic Syndrome I : Introduction01:24

Nephrotic Syndrome I : Introduction

Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of fluid...
Renal Corpuscle01:20

Renal Corpuscle

The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
Glycosaminoglycans01:23

Glycosaminoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...