The protective role of fucosylated chondroitin sulfate, a distinct glycosaminoglycan, in a murine model of streptozotocin-induced diabetic nephropathy

Autor: Gabriela Guimarães, Cristina L. Leão, André Luis Barreira, Conrado Rodrigues Gomes, Maurilo Leite, Alvimar G. Delgado, Rodrigo S. Fortunato, Paulo A.S. Mourão, Christina Maeda Takiya, Carolina Venturotti, Roberto J. C. Fonseca
Rok vydání: 2014
Předmět:
Male
Kidney Glomerulus
Glycobiology
lcsh:Medicine
Kidney
Biochemistry
Glycosaminoglycan
Diabetic nephropathy
chemistry.chemical_compound
Endocrinology
Medicine and Health Sciences
Diabetic Nephropathies
lcsh:Science
Glycosaminoglycans
Mammals
Histological Examination
Multidisciplinary
biology
Glomerular basement membrane
Messenger RNA
Chondroitin Sulfates
Drugs
Heparan sulfate
medicine.anatomical_structure
Bioassays and Physiological Analysis
Nephrology
Vertebrates
Collagen
Anatomy
Chondroitin
medicine.drug
Research Article
medicine.medical_specialty
Histology
Wistar Rats
Perlecan
Research and Analysis Methods
Rodents
Streptozocin
Diabetes Mellitus
Experimental
Internal medicine
medicine
Renal Diseases
Albuminuria
Animals
Animal Models of Disease
Rats
Wistar
Immunohistochemistry Techniques
Diabetic Endocrinology
Pharmacology
Renal Analysis
Biology and life sciences
Heparin
lcsh:R
Organisms
Streptozotocin
medicine.disease
Rats
Histochemistry and Cytochemistry Techniques
chemistry
Proteoglycan
Cytoprotection
biology.protein
Animal Studies
RNA
lcsh:Q
Microalbuminuria
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 9, p e106929 (2014)
ISSN: 1932-6203
Popis: Background Heparanase-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). Methods Diabetes 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. Results Treatment 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. Conclusions Our 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.
Databáze: OpenAIRE
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