title: Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology.
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.
authors: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Joost F M
authors: JF
authors: Lensen
authors: Nephrology Research Laboratory, Radboud Institute for Molecular Life Sciences, Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Johan
authors: J
authors: van der Vlag
authors: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Elly M M
authors: EM
authors: Versteeg
authors: Nephrology Research Laboratory, Radboud Institute for Molecular Life Sciences, Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jack F M
authors: JF
authors: Wetzels
authors: Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Lambert P W J
authors: LP
authors: van den Heuvel
authors: Nephrology Research Laboratory, Radboud Institute for Molecular Life Sciences, Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jo H M
authors: JH
authors: Berden
authors: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Toin H
authors: TH
authors: van Kuppevelt
authors: Nephrology Research Laboratory, Radboud Institute for Molecular Life Sciences, Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Angelique L W M M
authors: AL
authors: Rops
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D003871:Dermatan Sulfate