Regulation of Rat Glomerular Epithelial Cell Proteoglycans by High-Glucose Medium

Kasinath, Balakuntalam S.; Block, Joel A.; Singh, Ashok K.; Terhune, W. C.; Maldonado, Robert; Davalath, S.; Kallgren, M. J.; Wanna, Linda

doi:10.1006/abbi.1994.1097

Cited by 12 publications

(10 citation statements)

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“…Bovine GEndo glycoconjugates were systematically analyzed employing methods previously described (8, 12, 13). …”

Section: Methodsmentioning

confidence: 99%

“…Proteoglycans in each peak of Sepharose CL-4B chromatography were divided into three aliquots, and subjected to chondroitinase-ABC or nitrous acid digestion as previously described (8, 12); the third untreated aliquot served as a control. These conditions of have been shown to take enzymatic digestions to completion (8, 12, 13).…”

Section: Methodsmentioning

confidence: 99%

“…These conditions of have been shown to take enzymatic digestions to completion (8, 12, 13). Following GAG digestion gel chromatography was performed using a G:50 Sephadex column with PBS as the elution buffer and relative proportions of chondroitin/dermatan sulfate and heparan sulfate GAGs were determined.…”

Section: Methodsmentioning

confidence: 99%

“…Previous reports have shown that glomerular epithelial cells contribute to HSPG present in glomerular basement membrane (5-7). Incubation of glomerular epithelial cells in medium containing high glucose concentraion results in inhibition of synthesis of basement membrane HSPG, perlecan (8) or agrin (9). High glucose medium induced reduction in synthesis of perlecan was found to be mediated by regulation of gene expression of perlecan core protein (10), suggesting a role for glomerular epithelial cells in pathogenesis of proteinuria in diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Glomerular Endothelial Cell Proteoglycans by Glucose

Duraisamy

Faulkner

et al. 2004

J Korean Med Sci

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The presence of heparan sulfate proteoglycan (HSPG) in anionic sites in the lamina rara interna of glomerular basement membrane suggests that the proteoglycan may be deposited by the glomerular endothelial cells (GEndo). We have previously demonstrated that bovine GEndo in vitro synthesize perlecan, a species of glomerular basement membrane HSPG. In this study we examined whether high glucose medium regulates the GEndo metabolism of glycopeptides including perlecan. Metabolic labeling of glycoconjugates with 35S-SO4, sequential ion exchange and Sepharose CL-4B chromatography of labeled glycoconjugates, and northern analysis were performed. Incubation of GEndo for 8 to 14 weeks (but not for 1-2 weeks) in medium containing 30 mM glucose resulted in nearly 50% reduction in the synthesis of cell layer and medium 35SO4-labeled low anionic glycoproteins and proteoglycans, including that of basement membrane HSPG (Kav 0.42) compared to GEndo grown in 5 mM glucose medium; no changes in anionic charge density or hydrodynamic size of proteoglycans were noted. Northern analysis demonstrated that the mRNA abundance of perlecan was reduced by 47% in cells incubated with 30 mM glucose. Our data suggest that high glucose medium reduces the GEndo synthesis of perlecan by regulating its gene expression. Reduced synthesis of perlecan by GEndo may contribute to proteinuria seen in diabetic nephropathy.

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“…Bovine GEndo glycoconjugates were systematically analyzed employing methods previously described (8, 12, 13). …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Glomerular Endothelial Cell Proteoglycans by Glucose

Duraisamy

Faulkner

et al. 2004

J Korean Med Sci

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“…Similarly, exposure of cultured podocytes to high glucose increases the expression of collagen type IV (α3, α5 chains) and fibronectin [152], while it reduces the expression of HSPG [153] and its core protein agrin [154]. The effect of high glucose on collagen type IV α5 chain is mediated by a p38-dependent-TGF-β-independent pathway [155].…”

Section: Extracellular Matrix Depositionmentioning

confidence: 99%

Insight on the Pathogenesis of Diabetic Nephropathy from the Study of Podocyte and Mesangial Cell Biology

Gruden¹,

Perin²,

Camussi

2005

CDR

103

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Diabetic nephropathy is characterised by increased glomerular permeability to proteins, thickening of the glomerular basement membrane, and excessive extracellular matrix accumulation in the mesangium. Both mesangial cells and podocytes play a pivotal role in the pathogenesis of these alterations. Recent studies have cast light on both the mediators and the intracellular signalling molecules whereby high glucose and stretch, mimicking glomerular capillary hypertension, induce an abnormal extracellular matrix deposition. Furthermore, they have provided a better understanding of the mechanisms by which multiple pathways of hyperglycaemia- and hypertension-induced damage may converge at the cellular level. Glomerulosclerosis only partially explains the development of proteinuria and in recent years there has been a growing interest on the potential role of podocytes. The discovery of nephrin, a key molecule of the slit-diaphragm, has stressed the importance of podocytes in maintaining the glomerular size-selective barrier. Nephrin is lost in both human and experimental diabetic nephropathy and studies on cultured podocytes have shown that insults relevant to diabetes, such as high glucose, AGE, angiotensin II, and stretch, have important deleterious effects on podocyte survival and adhesion. This review focuses on the most significant advances in understanding the pathophysiology of both mesangial cells and podocytes, and their potential impact on diabetic nephropathy future treatments.

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Regulation of basement membrane heparan sulfate proteoglycan, perlecan, gene expression in glomerular epithelial cells by high glucose medium

et al. 1996

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Proteinuria in diabetic nephropathy has been correlated with reduction in heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane. We have previously shown that the underlying mechanism probably involves reduction in the synthesis by glomerular epithelial cells. In this study we explored whether high glucose medium regulates basement membrane HSPG gene expression. Northern analysis demonstrated that rat glomerular epithelial cells in vitro constitutively express mRNA for basement membrane HSPG, similar to that observed in rat kidney glomerulus. RNase protection assay showed that incubation of glomerular epithelial cells with 30 mM glucose for 24 h and 7 days resulted in reduction in HSPG mRNA abundance. The decrease in mRNA abundance correlated with reduction in the synthesis of 35SO4-labeled basement membrane HSPG as measured by immunoprecipitation. Reduction in synthesis of HSPG could not be entirely accounted for by decrease in mRNA abundance, suggesting both transcriptional and posttranscriptional mechanisms may be involved in reduction of glomerular basement membrane HSPG synthesis by glomerular epithelial cells in diabetic nephropathy.

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Regulation of Rat Glomerular Epithelial Cell Proteoglycans by High-Glucose Medium

Cited by 12 publications

References 0 publications

Regulation of Glomerular Endothelial Cell Proteoglycans by Glucose

Regulation of Glomerular Endothelial Cell Proteoglycans by Glucose

Insight on the Pathogenesis of Diabetic Nephropathy from the Study of Podocyte and Mesangial Cell Biology

Regulation of basement membrane heparan sulfate proteoglycan, perlecan, gene expression in glomerular epithelial cells by high glucose medium

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