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

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...

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Bibliographic Details
Published in:Kidney international 1996-04, Vol.49 (4), p.1079-1089
Main Authors: van Det, Nicole F., van den Born, Jacob, Tamsma, Jouke T., Verhagen, Nicole A.M., Berden, Jo H.M., Bruijn, Jan A., Daha, Mohamed R., van der Woude, Fokko J.
Format: Article
Language:English
Subjects:
Adult
Antibodies, Monoclonal
Associated diseases and complications
Biological and medical sciences
Cells, Cultured - drug effects
Cells, Cultured - metabolism
Chromatography, Gel
Chromatography, High Pressure Liquid
Dextrans
Diabetes. Impaired glucose tolerance
Dose-Response Relationship, Drug
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Enzyme-Linked Immunosorbent Assay
Epithelial Cells
Epithelium - metabolism
Ethanolamines
Fluorescent Antibody Technique
Gels
Glomerular Mesangium - cytology
Glomerular Mesangium - metabolism
Glucosamine - analysis
Glucosamine - metabolism
Glucose - pharmacology
Heparan Sulfate Proteoglycans
Heparitin Sulfate - analysis
Heparitin Sulfate - biosynthesis
Heparitin Sulfate - immunology
Humans
Leucine - metabolism
Medical sciences
Nitrites - pharmacology
Proteoglycans - analysis
Proteoglycans - biosynthesis
Proteoglycans - immunology
Sodium Radioisotopes - metabolism
Sulfates - analysis
Sulfates - metabolism
Tritium - metabolism
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Summary: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.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.1996.157