Primary human glomerular endothelial cells produce proteoglycans, and puromycin affects their posttranslational modification

Björnson, Anna; Moses, Jonatan; Ingemansson, Annika; Haraldsson, Börje; Sörensson, Jenny

doi:10.1152/ajprenal.00202.2004

Cited by 44 publications

(57 citation statements)

References 51 publications

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“…More recently, focus has shifted to the podocytes, since several novel proteins in the podocyte slit diaphragm have been found to be important for the barrier function [1][2][3]. In addition, we have suggested a role for the glomerular endothelial cell glycocalyx [4][5][6][7][8][9][10], an idea supported also by others [11,12].…”

Section: Introductionsupporting

confidence: 73%

“…Versican is an extracellular matrix proteoglycan with chondroitin sulphate chains that are able to bind hyaluronic acid [44]. We have recently found it to be expressed by human glomerular endothelial cells [10] and versican is most likely a component of the endothelial cell glycocalyx. Furthermore, in previous studies we have shown that digestion of hyaluronic acid and/or chondroitin sulphate in the glomerular endothelial cell glycocalyx increases the fractional clearance for albumin [9,43].…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that human glomerular endothelial cells produce several different proteoglycans [10] and that hyaluronan and/or chondroitin sulphate in the glomerular endothelial cell glycocalyx are important to maintain charge-selective properties in the barrier [9]. In diabetic nephropathy, studies have suggested that decreased synthesis of heparan sulphate proteoglycans [27][28][29][30] such as perlecan [31] is the reason for altered barrier function.…”

Section: Introductionmentioning

confidence: 99%

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Functional and molecular alterations of the glomerular barrier in long-term diabetes in mice

et al. 2006

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Aims/hypothesis Despite the fact that diabetic nephropathy is an increasingly common disorder that may lead to uraemia, the underlying mechanisms are still poorly understood and there is no specific therapy. To clarify whether long-term diabetes alters glomerular size-or charge-selectivity or both, we studied non-obese diabetic mice for up to 40 weeks. Materials and methods During the study period, spot urine was collected and blood pressure measured. At weeks 10 and 40, the right kidney was isolated and perfused at 8°C to inhibit tubular function, allowing for analysis of glomerular selectivity with albumin and Ficoll clearance. The left kidney was removed for further investigation using electron microscopy and molecular biology. Real-time PCR with low-density arrays was done to evaluate renal cortex mRNA expression of proteoglycans and other components in the glomerular barrier. After 40 weeks of diabetes, kidneys showed morphological changes typical of diabetic complications. Results At 40 weeks, the fractional clearance for negatively charged albumin was three times higher in the diabetic animals (0.0160) than in controls (0.0051, p<0.001), while fractional clearance for neutral Ficoll 35.5 Å with a Stokes Einstein radius similar to that of albumin was unaffected. In addition, protein and mRNA levels for versican and decorin were downregulated after 40 weeks of diabetes. Conclusions/interpretation We conclude that glomerular charge-but not size-selectivity was impaired in the diabetic animals with proteinuria. Also, glomerular components such as versican, decorin and fibromodulin were found to be downregulated after 40 weeks of diabetes.

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Section: Introductionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional and molecular alterations of the glomerular barrier in long-term diabetes in mice

et al. 2006

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“…21,22 The differences between our study and previous studies could simply be due to differences in the antibody affinity or to the examination of different stages of renal disease. In addition, the functional role or roles of biglycan are unclear; roles have been proposed in the maintenance of the glomerular charge barrier, 48,49 in the regulation of mesangial cell growth and survival, 50 in the regulation of TGF-␤ activity, 51 in the regulation of inflammation via activation of Toll-like receptors, 52 in the regulation of the assembly of connective tissues, 53 and in the structural composition of fibrosis, 22 among others. Both biglycan and decorin can bind TGF-␤, leading to its sequestration and neutralization of activity.…”

Section: Discussionmentioning

confidence: 99%

Renal Accumulation of Biglycan and Lipid Retention Accelerates Diabetic Nephropathy

Thompson

Wilson

Brandewie

et al. 2011

The American Journal of Pathology

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Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy.

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“…The second protein identified was LG3, the C-terminal domain of Perlecan, a proteoglycan found in the filtration barrier and expressed in all basement membranes (41,42). Although Perlecan has a proangiogenic role (43), its domain V, C-terminal fragment Endorepellin has potent antiangiogenic properties (44), providing it with a potential role in the development of a relatively avascular scar tissue that partially leads to progressive renal damage.…”

Section: Discussionmentioning

confidence: 99%

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

Rocchetti

Papale

d'Apollo

et al. 2013

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease. Design, setting, participants, & measurements Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007. Results Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig κ light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free κ light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free κ light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort. Conclusions Laminin G-like 3 and free κ light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.

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Primary human glomerular endothelial cells produce proteoglycans, and puromycin affects their posttranslational modification

Cited by 44 publications

References 51 publications

Functional and molecular alterations of the glomerular barrier in long-term diabetes in mice

Functional and molecular alterations of the glomerular barrier in long-term diabetes in mice

Renal Accumulation of Biglycan and Lipid Retention Accelerates Diabetic Nephropathy

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

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