Reduced Sulfation of Chondroitin Sulfate but Not Heparan Sulfate in Kidneys of Diabetic db/db Mice

Reine, Trine M.; Grøndahl, Frøy; Jenssen, Trond; Hadler‐Olsen, Elin; Prydz, Kristian; Kolset, Svein Olav

doi:10.1369/0022155413494392

Cited by 17 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculate that it was a transcriptional response to a post-translational reduction in renal content of chondroitin/dermatan sulfate or in the degree of sulfation of chondroitin sulfate chains, which has been already described in experimental DN [53], [54]. Gene expression analysis of other important PG core proteins also revealed interesting results.…”

Section: Discussionsupporting

confidence: 59%

The Protective Role of Fucosylated Chondroitin Sulfate, a Distinct Glycosaminoglycan, in a Murine Model of Streptozotocin-Induced Diabetic Nephropathy

et al. 2014

View full text Add to dashboard Cite

BackgroundHeparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS) have been described in diabetic nephropathy (DN). Glycosaminoglycan (GAG)-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS), a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX).MethodsDiabetes mellitus (DM) was induced by streptozotocin in male Wistar rats divided into three groups: DM (without treatment), FCS (8 mg/kg), and ENX (4 mg/kg), administered subcutaneously. After 12 weeks, we measured blood glucose, blood pressure, albuminuria, and renal function. The kidneys were evaluated for mesangial expansion and collagen content. Immunohistochemical quantifications of macrophages, TGF-β, nestin and immunofluorescence analysis of heparanase-1 and glomerular basement membrane (GBM) HS content was also performed. Gene expression of proteoglycan core proteins and enzymes involved in GAG assembly/degradation were analyzed by TaqMan real-time PCR.ResultsTreatment with GAGs prevented albuminuria and did not affect the glucose level or other functional aspects. The DM group exhibited increased mesangial matrix deposition and tubulointerstitial expansion, and prevention was observed in both GAG groups. TGF-β expression and macrophage infiltration were prevented by the GAG treatments, and podocyte damage was halted. The diabetic milieu resulted in the down-regulation of agrin, perlecan and collagen XVIII mRNAs, along with the expression of enzymes involved in GAG biosynthesis. Treatment with FCS and ENX positively modulated such changes. Heparanase-1 expression was significantly reduced after GAG treatment without affecting the GBM HS content, which was uniformly reduced in all of the diabetic animals.ConclusionsOur results demonstrate that the administration of FCS prevented several pathological features of ND in rats. This finding should stimulate further research on GAG treatment for this complication of diabetes.

show abstract

Section: Discussionsupporting

confidence: 59%

The Protective Role of Fucosylated Chondroitin Sulfate, a Distinct Glycosaminoglycan, in a Murine Model of Streptozotocin-Induced Diabetic Nephropathy

et al. 2014

View full text Add to dashboard Cite

show abstract

“…While HSPGs are the dominating species in kidney, CSPGs are expressed to a smaller degree, and changes in these structures might not be obvious until more overt changes in kidney functions take place. Notably, in diabetic mouse kidney we have observed a reduced sulfation of CS but not HS [49]. …”

Section: Discussionmentioning

confidence: 99%

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Reine

Kolseth

Meen

et al. 2015

Diabetes Research and Clinical Practice

View full text Add to dashboard Cite

Aims Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9–12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. Methods Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass–spectrometry. Results The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. Conclusions Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

show abstract

“…GAG(s) play an important physiological role as PG and are associated with other common diseases such as osteoarthritis (OA) [ 28 - 31 ], ligament injury or trauma in the knee [ 32 , 33 ], spinal cord injury [ 34 - 36 ], and diabetes mellitus (DM) [ 37 - 39 ]. GAG assay by tandem mass spectrometry should be applied to diagnosis, prognosis, and therapeutic efficacy of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Assay for Glycosaminoglycans by Tandem Mass Spectrometry and its Applications

TadaoOrii¹

2014

J Anal Bioanal Tech

View full text Add to dashboard Cite

Glycosaminoglycans (GAGs) are distributed in the whole body and play a variety of important physiological roles associated with inflammation, growth, coagulation, fibrinolysis, lipolysis, and cell-matrix biology. Accumulation of undegraded GAGs in lysosomes gives rise to a distinct clinical syndrome, mucopolysaccharidoses. Measurement of each specific GAG in a variety of specimens is urgently required to understand GAG interaction with other molecules, physiological status of patients, and prognosis and pathogenesis of the disease. We established a highly sensitive and accurate tandem mass spectrometry (LC-MS/MS) method for measurements of disaccharides derived from four specific GAGs [dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)]. Disaccharides were produced by specific enzyme digestion of each GAG, and quantified by negative ion mode of multiple reaction monitoring. Subclasses of HS and GAGs with identical molecular weights can be separated using a Hypercarbcolumn (2.0 mm×50 mm, 5 μm) with an aectonitrile gradient in ammonium acetate (pH 11.0). We also developed a GAG assay by RapidFire with tandem mass spectrometry (RF-MS/MS). The RF system consists of an integrated solid phase extraction robot that binds and de-salts samples from assay plates and directly injects them into a MS/MS detector, reducing sample processing time to ten seconds. RF-MS/MS consequently yields much faster throughput than conventional LC-MS/MS-based methods. However, the RF system does not have a chromatographic step, and therefore, cannot distinguish GAGs that have identical molecular weights. Both methods can be applied to analysis of dried blood spots, blood, and urine specimens. In this article, we compare the assay methods for GAGs and describe their potential applications.

show abstract

Reduced Sulfation of Chondroitin Sulfate but Not Heparan Sulfate in Kidneys of Diabetic db/db Mice

Cited by 17 publications

References 46 publications

The Protective Role of Fucosylated Chondroitin Sulfate, a Distinct Glycosaminoglycan, in a Murine Model of Streptozotocin-Induced Diabetic Nephropathy

The Protective Role of Fucosylated Chondroitin Sulfate, a Distinct Glycosaminoglycan, in a Murine Model of Streptozotocin-Induced Diabetic Nephropathy

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Assay for Glycosaminoglycans by Tandem Mass Spectrometry and its Applications

Contact Info

Product

Resources

About