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Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology.

Lensen JF, van der Vlag J, Versteeg EM, Wetzels JF, van den Heuvel LP, Berden JH, van Kuppevelt TH, Rops AL - PLoS ONE (2015)

Bottom Line: 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.Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients.Further research is required to delineate the exact role of different DS domains in renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

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.

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Related in: MedlinePlus

Expression of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by the antibodies LKN1 (A-D) and GD3A12 (E-H), type I collagen (I-L), decorin (M-P) and TGF-β (Q-T) in renal allograft rejection and controls.Representative photographs showing the expression of the 4/2,4-di-O-sulfated DS domain defined by LKN1 in the control human kidneys (A). Tubular interstitial expression of this 4/2,4-di-O-sulfated DS domain defined by LKN1 was increased in acute interstitial (B) and acute vascular (C) renal allograft rejections compared to interstitial fibrosis and tubular atrophy (IF/TA) (D). Expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 was similar in the control human kidney and the three types of renal allograft rejection (E-H), while expression of type I collagen (coll I) and decorin was increased in IF/TA (L, P) compared to the control human kidney (I, M), and acute interstitial (J, N) and acute vascular renal allograft rejections (K, O). Glomerular expression of transforming growth factor beta (TGF-β) was increased in the three types of renal allograft rejection (R-T) compared to the control human kidney (Q). Magnification A-P 100x, magnification Q-T 200x.
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pone.0134946.g001: Expression of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by the antibodies LKN1 (A-D) and GD3A12 (E-H), type I collagen (I-L), decorin (M-P) and TGF-β (Q-T) in renal allograft rejection and controls.Representative photographs showing the expression of the 4/2,4-di-O-sulfated DS domain defined by LKN1 in the control human kidneys (A). Tubular interstitial expression of this 4/2,4-di-O-sulfated DS domain defined by LKN1 was increased in acute interstitial (B) and acute vascular (C) renal allograft rejections compared to interstitial fibrosis and tubular atrophy (IF/TA) (D). Expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 was similar in the control human kidney and the three types of renal allograft rejection (E-H), while expression of type I collagen (coll I) and decorin was increased in IF/TA (L, P) compared to the control human kidney (I, M), and acute interstitial (J, N) and acute vascular renal allograft rejections (K, O). Glomerular expression of transforming growth factor beta (TGF-β) was increased in the three types of renal allograft rejection (R-T) compared to the control human kidney (Q). Magnification A-P 100x, magnification Q-T 200x.

Mentions: The distribution of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains recognized by, respectively, the LKN1 and GD3A12 antibody was analysed in biopsies with renal allograft rejection and controls (Figs 1 and 2). Relevant clinical data of the patients are given in Table 1. In controls, the 4/2,4-di-O-sulfated DS domain defined by LKN1 was expressed in the tubular interstitium, including the matrix surrounding Bowman’s capsule, with a distinct fibrillar expression pattern (Fig 1A). No expression inside the glomerulus was seen. Previously, we showed that this DS domain co-localized with type I collagen [20].


Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology.

Lensen JF, van der Vlag J, Versteeg EM, Wetzels JF, van den Heuvel LP, Berden JH, van Kuppevelt TH, Rops AL - PLoS ONE (2015)

Expression of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by the antibodies LKN1 (A-D) and GD3A12 (E-H), type I collagen (I-L), decorin (M-P) and TGF-β (Q-T) in renal allograft rejection and controls.Representative photographs showing the expression of the 4/2,4-di-O-sulfated DS domain defined by LKN1 in the control human kidneys (A). Tubular interstitial expression of this 4/2,4-di-O-sulfated DS domain defined by LKN1 was increased in acute interstitial (B) and acute vascular (C) renal allograft rejections compared to interstitial fibrosis and tubular atrophy (IF/TA) (D). Expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 was similar in the control human kidney and the three types of renal allograft rejection (E-H), while expression of type I collagen (coll I) and decorin was increased in IF/TA (L, P) compared to the control human kidney (I, M), and acute interstitial (J, N) and acute vascular renal allograft rejections (K, O). Glomerular expression of transforming growth factor beta (TGF-β) was increased in the three types of renal allograft rejection (R-T) compared to the control human kidney (Q). Magnification A-P 100x, magnification Q-T 200x.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4556443&req=5

pone.0134946.g001: Expression of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by the antibodies LKN1 (A-D) and GD3A12 (E-H), type I collagen (I-L), decorin (M-P) and TGF-β (Q-T) in renal allograft rejection and controls.Representative photographs showing the expression of the 4/2,4-di-O-sulfated DS domain defined by LKN1 in the control human kidneys (A). Tubular interstitial expression of this 4/2,4-di-O-sulfated DS domain defined by LKN1 was increased in acute interstitial (B) and acute vascular (C) renal allograft rejections compared to interstitial fibrosis and tubular atrophy (IF/TA) (D). Expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 was similar in the control human kidney and the three types of renal allograft rejection (E-H), while expression of type I collagen (coll I) and decorin was increased in IF/TA (L, P) compared to the control human kidney (I, M), and acute interstitial (J, N) and acute vascular renal allograft rejections (K, O). Glomerular expression of transforming growth factor beta (TGF-β) was increased in the three types of renal allograft rejection (R-T) compared to the control human kidney (Q). Magnification A-P 100x, magnification Q-T 200x.
Mentions: The distribution of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains recognized by, respectively, the LKN1 and GD3A12 antibody was analysed in biopsies with renal allograft rejection and controls (Figs 1 and 2). Relevant clinical data of the patients are given in Table 1. In controls, the 4/2,4-di-O-sulfated DS domain defined by LKN1 was expressed in the tubular interstitium, including the matrix surrounding Bowman’s capsule, with a distinct fibrillar expression pattern (Fig 1A). No expression inside the glomerulus was seen. Previously, we showed that this DS domain co-localized with type I collagen [20].

Bottom Line: 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.Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients.Further research is required to delineate the exact role of different DS domains in renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus