Abstract
Dermatan sulfate (DS), also known as chondroitin sulfate (CS)-B, is a member of the linear polysaccharides called glycosaminoglycans (GAGs). The expression of CS/DS and DS proteoglycans is increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial sclerosis and nephrosclerosis. Little, however, is known about structural alterations in DS in renal diseases. The aim of this study was to evaluate the renal expression of two different DS domains in renal transplant rejection and glomerular pathologies. DS expression was evaluated in normal renal tissue and in kidney biopsies obtained from patients with acute interstitial or vascular renal allograft rejection, patients with interstitial fibrosis and tubular atrophy (IF/TA), and from patients with focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy (MGP) or systemic lupus erythematosus (SLE), using our unique specific anti-DS antibodies LKN1 and GD3A12. Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE. Importantly, all patients showed glomerular LKN1 staining in contrast to the controls. Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients. Our data suggest a role for the DS domain recognized by antibody LKN1 in renal diseases with early fibrosis. Further research is required to delineate the exact role of different DS domains in renal fibrosis.
Highlights
Dermatan sulfate (DS) is a member of the large family of linear polysaccharides called glycosaminoglycans (GAGs)
chondroitin sulfate (CS)/DS and DSPGs have been reported to be increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial sclerosis and nephrosclerosis [14, 15]
This study shows the differential expression of the specific 4/2,4-di-O-sulfated and iduronic acid (IdoA)-GalNAc4S DS domains recognized by the anti-DS antibodies LKN1 and GD3A12, respectively, in normal kidney and in renal pathology
Summary
Dermatan sulfate (DS) is a member of the large family of linear polysaccharides called glycosaminoglycans (GAGs). DS is known as chondroitin sulfate B (CS-B) and is composed of repeating disaccharide units consisting of N-acetyl galactosamine (GalNAc) and glucuronic acid (GlcA) residues. The presence of the epimerized form of GlcA, iduronic acid (IdoA), PLOS ONE | DOI:10.1371/journal.pone.0134946. The level of complexity of DS is dictated by a variable structure and chain length of up to 40–100 disaccharide units. The uronic acid can be either a GlcA or IdoA with or without 2-O-sulfation, and the GalNAc residue can be 4- and/or 6-O-sulfated. These possibilities can result in the formation of several defined disaccharide units; CSA (4-Osulfated), CSB/DS (IdoA and 2,4-di-O-sulfated), CSC (6-O-sulfated), CSD (2,6-di-O-sulfated), CSE (4,6-di-O-sulfated) and CSEi (IdoA and 4,6-di-O-sulfated) [3]
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