Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells

Autor: N. A. M. Verhagen, F. J. Van Der Woude, Jouke T. Tamsma, Jhm Berden, N.F. van Det, J. A. Bruijn, J. van den Born, M. R. Daha
Přispěvatelé: Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT)
Jazyk: angličtina
Předmět:
Fluorescent Antibody Technique
Epithelium
chemistry.chemical_compound
Sulfation
Monoclonal
Leucine/metabolism
Cultured/drug effects
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Cells
Cultured
Chromatography
High Pressure Liquid
Glucosamine
Chromatography
Gel
Mesangial cell
biology
Sulfates
Glomerular basement membrane
Antibodies
Monoclonal
Proteoglycans/analysis
Dextrans
Nitrites/pharmacology
Heparan sulfate
Glucosamine/analysis
Glucose/pharmacology
Glomerular Mesangium
medicine.anatomical_structure
Heparitin Sulfate/analysis
Ethanolamines
Nephrology
High Pressure Liquid
Chromatography
Gel
Proteoglycans
Drug
Cells
Cultured/drug effects
Adult
medicine.medical_specialty
Tritium/metabolism
Cells
Enzyme-Linked Immunosorbent Assay
Perlecan
Tritium
Antibodies
Dermatan sulfate
Dose-Response Relationship
Sodium Radioisotopes/metabolism
Leucine
Glomerular Mesangium/cytology
Internal medicine
medicine
Humans
Sulfates/analysis
Nitrites
Dose-Response Relationship
Drug
Sodium Radioisotopes
Epithelial Cells
Epithelium/metabolism
carbohydrates (lipids)
Glucose
Endocrinology
chemistry
Proteoglycan
Chondroitin sulfate proteoglycan
biology.protein
Heparitin Sulfate
Gels
Heparan Sulfate Proteoglycans
Zdroj: Kidney International. Supplement, 49, 1079-1089
Kidney International. Supplement, 49, 4, pp. 1079-1089
Kidney International, 49(4), 1079-1089. ELSEVIER SCIENCE INC
ISSN: 0085-2538
DOI: 10.1038/ki.1996.157
Popis: Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells. Changes in heparan sulfate metabolism may be important in the pathogenesis of diabetic nephropathy. Recent studies performed on renal biopsies from patients with diabetic nephropathy revealed a decrease in heparan sulfate glycosaminoglycan staining in the glomerular basement membrane without changes in staining for heparan sulfate proteoglycan-core protein. To understand this phenomenon at the cellular level, we investigated the effect of high glucose conditions on the synthesis of heparan sulfate proteoglycan by glomerular cells in vitro. Human adult mesangial and glomerular visceral epithelial cells were cultured under normal (5mM) and high glucose (25mM) conditions. Immunofluorescence performed on cells cultured in 25mM glucose confirmed and extended the in vivo histological observations. Using metabolic labeling we observed an altered proteoglycan production under high glucose conditions, with predominantly a decrease in heparan sulfate compared to dermatan sulfate or chondroitin sulfate proteoglycan. N-sulfation analysis of heparan sulfate proteoglycan produced under high glucose conditions revealed less di- and tetrasaccharides compared to larger oligosaccharides, indicating an altered sulfation pattern. Furthermore, with quantification of glomerular basement membrane heparan sulfate by ELISA, a significant decrease was observed when mesangial and visceral epithelial cells were cultured in high glucose conditions. We conclude that high glucose concentration induces a significant alteration of heparan sulfate production by mesangial cells and visceral epithelial cells. Changes in sulfation and changes in absolute quantities are both observed and may explain the earlier in vivo observations. These changes may be of importance for the altered integrity of the glomerular charge-dependent filtration barrier and growth-factor matrix interactions in diabetic nephropathy.
Databáze: OpenAIRE
Externí odkaz: