Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve control persons excreted 282 +/- 106 micrograms proteoglycans/l urine (+/- S.D.) in a random urine sample. For four patients with a clinical proteinuria of 1.1 to 5.8 g/l, the excretion varied between 52 and 387 micrograms/l. The control proteoglycan pattern in an electrophoretic analysis on polyacrylamide gel and stained with digoxigenin followed by incubation with digoxigenin antibodies, consisted of a major band with a molecular weight of 100,000. It comigrated with a similar band in the serum proteoglycan pattern. The control pattern contained also lighter fractions with molecular weights between 50,000 and 28,000. The major proteoglycan band remained unchanged in the pattern of the proteinuric patients while conspicuous new bands appeared in the pattern of patients with proteinuria greater than 1.9 g/l. They seem to be of urinary tract origin as they had no counterparts in the serum proteoglycan pattern.
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PMID:A sensitive method for the analysis of urinary proteoglycans. 148 89

In order to evaluate the pathogenesis of proteinuria and the charge of immune deposits in lupus nephritis, anionic sites of periodate-lysin-paraformaldehyde (PLP) fixed renal tissue (5 patients with renal pelvic tumor as normal control and 17 patients with lupus nephritis), were stained with the critical electrolyte concentration method. Cuprolinic blue (CB) was used as a cationic probe. Ultra-structural study and semi-quantitative analysis were done. In the normal glomerular basement membrane (GBM), the CB stainable anionic sites appeared as filamentous structure with several short lateral branches. On the basis of electron microscopic observation of isolated proteoglycan, it is suggested that the central filaments are the protein core and the branches are the glycosaminoglycans of proteoglycan molecules. These filamentous anionic sites were located mainly in the laminae larae and lie close to each other forming a mesh-like network pattern. The semi-quantitative analysis of the normal GBM revealed that the number of anionic sites in the lamina rara externa (LRE) was 22.9 +/- 1.9-23.7 +/- 1.4/1000 nm GBM and in the lamina rara interna (LRI) 14.0 +/- 1.6-15.1 +/- 1.5/1000 nm GBM. These findings suggest that the anionic sites composed of heparan sulphate proteoglycan occupy large area of the laminae larae and prevent permeation of anionic molecules. In non-proteinuric 5 patients with class II lupus nephritis, the number of anionic sites of the GBM (LRE; 21.3 +/- 2.0-22.3 +/- 1.8/1000 nm GBM, LRI; 13.5 +/- 2.0-14.2 +/- 2.0/1000 nm GBM) showed no significant difference from that of the normal GBM. In contrast, the GBM of proteinuric patients with class IV (6 patients, LRE; 14.8 +/- 2.7-19.3 +/- 1.8/aooo nm GBM, LRI; 5.8 +/- 1.9-11.3 +/- 2.4/1000 nm GBM) and (V) (6 patients, LRE; 13.0 +/- 2.4-17.9 +/- 2.8/1000 nm GBM, LRI; 12.0 +/- 1.9-13.0 +/- 2.5/1000 nm GBM) exhibited loss of the anionic sites in association with the localization of the immune deposits (ID). From these findings, it is concluded that in severe and active lupus nephritis the failure of charge barrier of the GBM is responsible for the proteinuria. The ID observed in the patients with lupus nephritis were not stained with CB. This finding suggests that net charge of the ID could be cationic and that cationic immune complex and/or antibody could involve in the pathogenesis of lupus nephritis.
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PMID:[Electron microscopic study of the glomerular basement membrane charge barrier and the charge of immune deposits in lupus nephritis]. 178 70

Dietary protein restriction has been shown to slow the rate of loss of kidney function in humans with progressive glomerulosclerosis due to glomerulonephritis or diabetes mellitus. A central feature of glomerulosclerosis is the pathological accumulation of extracellular matrix within the diseased glomeruli. Transforming growth factor beta 1 (TGF-beta 1) is known to have widespread regulatory effects on extracellular matrix and has been implicated as a major cause of increased extracellular matrix synthesis and buildup of pathological matrix within glomeruli in experimental glomerulonephritis. In the present study, it is shown that administration of a low protein diet to rats rapidly reduces the elevated expression of TGF-beta 1 mRNA and TGF-beta 1 protein that is known to occur within glomeruli after induction of glomerulonephritis. Compared to a normal protein diet, glomerulonephritic rats receiving the low protein diet did not develop an increase in glomerular extracellular matrix and showed significantly less proteinuria. Glomeruli isolated from glomerulonephritic rats fed the normal protein diet showed a marked increase in proteoglycan synthesis on day 7 of disease and were demonstrated to be secreting increased amounts of TGF-beta 1 into the medium, whereas glomeruli at the same point in time isolated from rats on a low protein diet showed no increase in proteoglycan production or TGF-beta 1 secretion. These results suggest that a mechanism of the rapid therapeutic effect of a low protein diet on experimental glomerulonephritis is through suppression of TGF-beta 1 expression and prevention of the induction of extracellular matrix synthesis within the injured glomeruli.
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PMID:Dietary protein restriction rapidly reduces transforming growth factor beta 1 expression in experimental glomerulonephritis. 194 1

Sulfated proteoglycans (fixed anionic sites) on the glomerular basement membrane (GBM) of kidneys from diabetic and nondiabetic patients have been demonstrated by electron microscopy using polycationic dyes (ruthenium red, polyethyleneimine). These substances were used for immersion fixation of renal biopsy specimens. The thickened GBM of diabetics revealed a reduced proteoglycan content within both the narrowed laminae rarae, where normally particles were seen at 60 nm intervals. Proteinuria was observed in all such cases, but no immunopathological alterations of the basement membranes were seen. With both tracer substances anionic sites were also demonstrated in different segments of the thickened lamina densa in diabetics. In polyethyleneimine-treated biopsies some segments of the membrane showed increased anionic moieties at the junction of the basement membrane and the epithelial and endothelial cell membranes. These are probably acid glycoproteins linked to the cell membrane and the synthesis of these basement membrane components may represent a compensatory mechanism seeking to restore normal permeability.
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PMID:Reduced content and abnormal distribution of anionic sites (acid proteoglycans) in the diabetic glomerular basement membrane. 242 79

We investigated nephritogenic potential of antibodies to heparan sulfate-proteoglycan of glomerular basement membrane. Glomeruli were isolated, basement membranes were prepared, proteoglycans extracted, and purified core protein was obtained. We immunized rabbits with the core protein, IgG fraction prepared from the antisera and specificity of the antibody determined. A single immunoprecipitin line in agar diffusion plate and a single band (approximately 18,000 mol wt) on the immunoblot autoradiograms were visualized. The antibody showed precise reactivity with the glomerular basement membranes. The clearance studies indicated that approximately 75% of the radioiodinated antibody disappeared from circulation within 1 h and 1-2% bound to the kidney. For nephritogenicity experiments, the antibody was intravenously administered into rats and we examined their kidneys at 1 h to 24 d later. A linear immunofluorescence of glomerular basement membranes was observed with rabbit IgG at all times while that of C3 until the 10th day. Early morphologic changes included glomerular infiltration of polymorphonuclear leukocytes with focal exfoliation of endothelium. The leukocytic infiltration subsided by the third day and was followed by progressive thickening of basement membranes, focal mesangial cell proliferation, increase in mesangial matrix, and accumulation of monocytes. Focal knob-like thickening of glomerular basement membrane was observed from the 15th day onward. Regularly-spaced electrondense deposits were seen in the lamina rara interna and externa of glomerular basement membranes and persisted throughout the investigatory period. No significant proteinuria was observed at any stage of the experiment. These findings suggest that the antibodies to the basement membrane heparan sulfate-proteoglycan are nephrotoxic but possess weak nephritogenic potential.
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PMID:Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane--I. 293 58

Antibodies to glomerular basement membrane, heparan sulfate-proteoglycans are nephrotoxic but possess a weak nephritogenic potential. In order to enhance the nephritogenic potential, the antibodies were intravenously administered into rats presensitized with heterologous rabbit IgG. This resulted in the integration of heterologous and autologous phases, the two phases characteristic of the traditional model of nephrotoxic serum nephritis. The presensitization caused a dramatic shift in the binding characteristics of the heterologous antibodies between the kidney and lymphoid tissues. A proliferative form of immune complex glomerulonephritis associated with a remarkable proteinuric response was observed. In addition, a moderate degree of hematuria was noted as well. The proteinuria was largely complement-dependent and may possibly be cell-mediated as well. The proteinuria became severe with increasing production of host IgG antibodies and with their subsequent sequestration in the glomeruli. The predominant glomerular lesions were in the form of epimembranous/subepithelial immune deposits, which became more frequent with timely increasing titer of host autologous IgG antibodies. These findings indicate that antibodies to heparan sulfate-proteoglycan, an authentic component of the basement membrane, are capable of mediating a glomerular injury with acquisition of nephritogenic potential in an appropriate environment of the host. At present, it seems that this is the sole constituent of the basement membrane whose antibodies are capable of inducing an immune complex nephritis.
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PMID:Nephritogenicity of proteoglycans. II. A model of immune complex nephritis. 297 59

The synthesis of intact proteoglycans and their glycosaminoglycan (GAG) side chains by isolated rat glomeruli in vitro were studied both at the onset (5 days) and at the point of maximal proteinuria (7 days) of the nephrotic syndrome induced with the aminonucleoside of puromycin. Glomeruli from nephrotic animals incorporated 1.5-fold and 3.0-fold more 35SO4 label into GAG than glomeruli from control animals at 5 and 7 days, respectively, with heparan-35SO4 GAG being responsible for the majority of the increment. Both nephrotic and control incubations contained 60% of the label in the incubation medium, 40% in the glomerular fractions, and less than 1% in the glomerular basement membrane. Glomerular basement membrane from nephrotic rats had no change in their total heparan-35SO4 GAG content. The majority of intact proteoglycan(s) from the glomerular matrix and from the incubation medium of nephrotic and control animals was found in the most buoyantly dense fraction of CsCl gradients (fraction 1). 35S-labeled material isolated from glomeruli of nephrotic animals showed a consistent shift toward lower density gradient fractions, indicating a decrease in their overall carbohydrate to protein ratio. Diethylaminoethyl chromatography of fraction 1 proteoglycan showed a single biphasic peak with the nephrotic rat having an increase in the proportion contributed by the earlier component of the peak. Fraction 1 proteoglycan(s) from the nephrotic experiment was found to have a smaller average hydrodynamic size by Sepharose CL-2B chromatography without a significant change in the corresponding 35S-GAG chain sizes (molecular weight 14,000) by Sepharose CL-6B chromatography. 35S-macromolecules from glomeruli of nephrotic and control rats that appeared in the middle of the CsCl gradients (fraction 3) had similar Sepharose CL-2B elution volumes, whereas the corresponding 35S-GAG chains from incubations of glomeruli from nephrotic animals were smaller. Increased synthesis of heparan sulfate proteoglycan by glomeruli from puromycin aminonucleoside-induced nephrotic rats may be compensatory to loss of another component of the glomerular filtration barrier or may result from abnormal interaction of proteoglycan(s) from nephrotic animals with other glomerular matrix constituents.
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PMID:Alterations in proteoglycan metabolism in the nephrotic syndrome induced by the aminonucleoside of puromycin. 623 22

Nephrosis is characterized by glomerular epithelial cell injury and a decrease in the glomerular basement membrane (GBM) proteoglycan content. Although CsA is a useful treatment for a group of patients with this disease, its mechanism of action is unclear. We have previously shown that in experimental nephrosis there is an increase in the glomerular production of tumour necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF). Here we have studied the effect of CsA on kidney generation of TNF-alpha and PAF in puromycin aminonucleoside (PAN) nephrosis as well as on the synthesis of proteoglycans by cultured glomerular epithelial cells. Rats receiving CsA had, on day 8 of PAN injection, a significant reduction in proteinuria, blood cholesterol levels and in interstitial mononuclear cells. A diminution in glomerular production and urinary excretion of TNF-alpha and PAF was also noted. In in vitro studies, at 24 h of incubation PAF and TNF-alpha induced in glomerular epithelial cells a significant decrease in proteoglycan synthesis. Neither PAF nor TNF-alpha had any significant effect on glomerular epithelial cell proliferation. CsA alone induced a dose-response increase in proteoglycan synthesis and a slight decrease in cell proliferation. CsA also reversed the inhibitory effect of PAF and TNF-alpha on proteoglycan synthesis. However, CsA did not alter the pattern of proteoglycan production, remaining around 50% chondroitinase ABC-, 15% heparitinase-sensitive. Our results indicate that PAF and TNF-alpha could be implicated in the pathogenesis of nephrosis through the inhibition of proteoglycan synthesis by glomerular epithelial cells. The beneficial effect of CsA in nephrosis may be due to the recovery of the GBM charge selectivity caused by the normalization of glomerular PAF and TNF-alpha synthesis and the increase in proteoglycan synthesis by glomerular epithelial cells.
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PMID:Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators and proteoglycans in experimental nephrosis. 853 80

Cadmium is widely used in industry, causing exposure of workers and environmental pollution because of its persistence in the biosystems. Its very long half-life in the human organism causes its accumulation over the lifetime in liver and kidneys. Cadmium ions have a high affinity for tissue thiols, induce the synthesis of a carrier cysteine-rich polypeptide called metallothionein, and impair proteoglycan metabolism. Significant renal effects include tubular nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia, and calcium wastage. Chronic sequels include decrease in the glomerular filtration rate and increased risk of kidney stone disease. Biological monitoring of cadmium absorption includes determination of urinary cadmium and of low molecular weight marker proteins, such as beta2-microglobulin or retinol binding protein, the tubular reabsorption of which is impaired before a frank proteinuria.
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PMID:Cadmium-associated renal disease. 857 Aug 61

There are currently no effective therapies for progressive fibrotic diseases. Recent evidence has implicated overproduction of transforming growth factor-beta1 (TGF-beta1) as a major cause of tissue fibrosis. Furthermore, this evidence implies that inhibitors of TGF-beta1 may be clinically useful as antifibrotic agents. The proteoglycan decorin is a known inhibitor of TGF-beta1. In a rat model of glomerulonephritis we have shown that fibrosis is mediated by TGF-beta1. We report here that transfer of decorin cDNA into rat skeletal muscle increases the amount of decorin messenger RNA and protein present in skeletal muscle and decorin present in kidney, where it has a marked therapeutic effect on fibrosis induced by glomerulonephritis. Transfected glomerulonephritic rats showed a significant reduction in levels of glomerular TGF-beta1 mRNA and TGF-beta1 protein, extracellular matrix accumulation and proteinuria. These results demonstrate the potential of gene therapy as a novel treatment for fibrotic diseases caused by TGF-beta1.
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PMID:Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. 859 51


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