Limits...
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.

No MeSH data available.


Related in: MedlinePlus

Semi-quantitative analysis of the expression the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12, type I collagen, decorin and TGF-β in the interstitium (A) and glomeruli (B) of patients with FSGS, MGP and SLE.Staining intensities of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12 respectively and of type I collagen, decorin and transforming growth factor beta (TGF-β) were scored using a scale of 0–4 and revealed a significantly increased expression of the 4/2,4-di-O-sulfated DS domain and type I collagen in the interstitium (A) and glomeruli (B) of patients with glomerular diseases. Glomerular expression of TGF-β also was increased in patients with glomerular diseases (B), while expression of the IdoA-Gal-NAc4S DS domain and decorin was similar in the interstitium (A) of patients and controls. *P<0.05 vs control.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556443&req=5

pone.0134946.g004: Semi-quantitative analysis of the expression the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12, type I collagen, decorin and TGF-β in the interstitium (A) and glomeruli (B) of patients with FSGS, MGP and SLE.Staining intensities of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12 respectively and of type I collagen, decorin and transforming growth factor beta (TGF-β) were scored using a scale of 0–4 and revealed a significantly increased expression of the 4/2,4-di-O-sulfated DS domain and type I collagen in the interstitium (A) and glomeruli (B) of patients with glomerular diseases. Glomerular expression of TGF-β also was increased in patients with glomerular diseases (B), while expression of the IdoA-Gal-NAc4S DS domain and decorin was similar in the interstitium (A) of patients and controls. *P<0.05 vs control.

Mentions: Since these 2 specific DS domains were differentially expressed in the different types of renal allograft rejection, we also analyzed their renal expression in three glomerular diseases FSGS, MGP and SLE. Relevant clinical data of these patients are given in Table 2. In all these glomerular diseases, the 4/2,4-di-O-sulfated DS domain, recognized by the LKN1 antibody (Fig 3B–3D), and type I collagen (Fig 3J–3L) were expressed in the glomerulus in contrast to the controls (Figs 3A, 3I, and 4B). Furthermore, expression of this DS domain was significantly increased in the tubular interstitium of patients with FSGS, MGP and SLE (Figs 3B–3D and 4A), which was accompanied by an increased expression of type I collagen as well (Figs 3J–3L and 4A). Expression of TGF-β was increased in the tubular interstitium of patients with FSGS and SLE (Figs 3R, 3T, and 4A). Importantly, the increased glomerular expression of the 4/2,4-di-O-sulfated DS domain was accompanied by an increased glomerular expression of TGF-β (Figs 3R–3T and 4B) compared to the controls (Figs 3Q and 4B). In contrast to the 4/2,4-di-O-sulfated DS domain, the IdoA-Gal-NAc4S DS domain, recognized by the antibody GD3A12, and decorin were not expressed in the glomeruli of patients with glomerular diseases (Fig 3F–3H and 3N–3P). Furthermore, the expression of the IdoA-Gal-NAc4S DS domain and decorin in the tubular compartment was similar in both normal and glomerular diseased kidneys (Figs 3E–3H, 3M–3P and 4A).


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)

Semi-quantitative analysis of the expression the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12, type I collagen, decorin and TGF-β in the interstitium (A) and glomeruli (B) of patients with FSGS, MGP and SLE.Staining intensities of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12 respectively and of type I collagen, decorin and transforming growth factor beta (TGF-β) were scored using a scale of 0–4 and revealed a significantly increased expression of the 4/2,4-di-O-sulfated DS domain and type I collagen in the interstitium (A) and glomeruli (B) of patients with glomerular diseases. Glomerular expression of TGF-β also was increased in patients with glomerular diseases (B), while expression of the IdoA-Gal-NAc4S DS domain and decorin was similar in the interstitium (A) of patients and controls. *P<0.05 vs control.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134946.g004: Semi-quantitative analysis of the expression the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12, type I collagen, decorin and TGF-β in the interstitium (A) and glomeruli (B) of patients with FSGS, MGP and SLE.Staining intensities of the 4/2,4-di-O-sulfated and IdoA-Gal-NAc4S DS domains defined by LKN1 and GD3A12 respectively and of type I collagen, decorin and transforming growth factor beta (TGF-β) were scored using a scale of 0–4 and revealed a significantly increased expression of the 4/2,4-di-O-sulfated DS domain and type I collagen in the interstitium (A) and glomeruli (B) of patients with glomerular diseases. Glomerular expression of TGF-β also was increased in patients with glomerular diseases (B), while expression of the IdoA-Gal-NAc4S DS domain and decorin was similar in the interstitium (A) of patients and controls. *P<0.05 vs control.
Mentions: Since these 2 specific DS domains were differentially expressed in the different types of renal allograft rejection, we also analyzed their renal expression in three glomerular diseases FSGS, MGP and SLE. Relevant clinical data of these patients are given in Table 2. In all these glomerular diseases, the 4/2,4-di-O-sulfated DS domain, recognized by the LKN1 antibody (Fig 3B–3D), and type I collagen (Fig 3J–3L) were expressed in the glomerulus in contrast to the controls (Figs 3A, 3I, and 4B). Furthermore, expression of this DS domain was significantly increased in the tubular interstitium of patients with FSGS, MGP and SLE (Figs 3B–3D and 4A), which was accompanied by an increased expression of type I collagen as well (Figs 3J–3L and 4A). Expression of TGF-β was increased in the tubular interstitium of patients with FSGS and SLE (Figs 3R, 3T, and 4A). Importantly, the increased glomerular expression of the 4/2,4-di-O-sulfated DS domain was accompanied by an increased glomerular expression of TGF-β (Figs 3R–3T and 4B) compared to the controls (Figs 3Q and 4B). In contrast to the 4/2,4-di-O-sulfated DS domain, the IdoA-Gal-NAc4S DS domain, recognized by the antibody GD3A12, and decorin were not expressed in the glomeruli of patients with glomerular diseases (Fig 3F–3H and 3N–3P). Furthermore, the expression of the IdoA-Gal-NAc4S DS domain and decorin in the tubular compartment was similar in both normal and glomerular diseased kidneys (Figs 3E–3H, 3M–3P and 4A).

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