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)

The perfused isolated kidney is a partial ischemic system that is characterised by glomerular proteinuria and release of glomerular heparan sulfate. Metabolic changes associated with the levels of glutathione, xanthine oxidase and glyceraldehyde 3-dehydrogenase indicated that oxygen radical metabolites were being produced during the perfusion. We have demonstrated that a mixture of oxygen metabolite scavengers containing mannitol, superoxide dismutase and catalase included in the perfusion medium significantly reduced protein excretion. Similar results were obtained with the administration of allopurinol to the rat 24h prior to kidney removal and allopurinol in the perfusion medium. [35S]Heparan sulfate loss from the glomerulus was totally inhibited by the scavenger mixture. These results suggest that reactive oxygen metabolites may be involved in damage to renal capillaries, specifically to heparan sulfate proteoglycan, which leads to proteinuria as a result of partial ischemia produced during perfusion.
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PMID:The inhibitory action of oxygen radical scavengers on proteinuria and glomerular heparan sulphate loss in the isolated perfused kidney. 214 Dec 55

We investigated the distribution of extracellular matrix components such as fibronectin, laminin, type III, IV, V, and VI collagens and heparan sulfate proteoglycan (HSPG) in normal and diseased glomeruli using the indirect immunofluorescence method. This study included 96 renal biopsies: 7 controls, 3 minimal change nephrotic syndrome (MCNS), 47 mesangial proliferative glomerulonephritis (PGN), 25 membranous nephropathy (MN) and 14 membranoproliferative glomerulonephritis (MPGN) including 3 lupus nephritis. Fibronectin was detected predominantly in the mesangium and less prominently in the glomerular basement membrane (GBM) of normal glomeruli. Laminin and type IV collagen were present in the mesangium and GBM, type III collagen in the interstitium, and type V collagen in the mesangium, interstitium and a part of GBM. Type VI collagen was observed in the mesangium, interstitium and slightly in GBM. Anti-HSPG antibody reacted with the mesangium and GBM. MCNS showed a distribution of these antigens similar to that in normal controls. The finding that staining for HSPG was not decreased in the GBM and mesangium indicated that there was no change in the core protein of HSPG. Fibronectin, laminin, type IV collagen and HSPG were increased in the thickened GBM of MN and in the expanded mesangium of PGN. In MPGN, these matrix components were increased in the mesangium and GBM with remarkable increase of type V and VI collagens. While type III collagen was not found in normal glomeruli, it became detectable in the mesangium and a part of GBM in MPGN. No significant decrease in the intensity of fluorescence for HSPG was observed in the glomeruli from nephrotic patients. These findings suggest that proteinuria might be caused by the structural alteration in the glycosaminoglycan portion of HSPG, changes in any anionic material other than HSPG, or both, and also indicate that the glomerular mesangial sclerosis is closely related to the increase of type V and VI collagens.
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PMID:Alterations in the extracellular matrix components in human glomerular diseases. 250 Jul 70

The isolated kidney perfused with modified Krebs-Henseleit buffer with amino acids yields heavy proteinuria associated with reduced ATP levels characteristic of partial ischemia. These conditions are associated with a similar perfusion time dependent release of degraded vascular [35S]heparan sulfate proteoglycan into the perfusate solution which included a 60% loss of [35S]macromolecular material from the glomerulus after 2h of perfusion. Small amounts of [35S]macromolecular material were found in the urine and lymph. These results demonstrate that partial ischemia promotes a specific response in the overall renal vasculature, probably involving oxygen reactive metabolites, that results in the preferential release of heparan sulphate from the basement membrane and endothelial cells on the luminal side of the capillary wall.
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PMID:Partial ischemia and proteinuria during isolated kidney perfusion is accompanied by the release of vascular [35S]heparan sulfate. 253 69

The distribution of heparan sulfate proteoglycan (HS-PG) was examined electron microscopically by the high iron diamine (HID) method in puromycin aminonucleoside (PAN) nephrosis, accelerated Masugi nephritis (NTN), and serum sickness nephritis induced by bovine serum albumin (BSA nephritis) in the rat. In PAN nephrosis rats, no change was observed in the distribution of HS-PG in the lamina rara externa (LRE) of the glomerular basement membrane (GBM) throughout the experiment. In NTN rats, however, the loss of HS-PG was observed, and it was associated with subepithelial electron dense deposits formed possibly by serum sickness mechanism, but not with inflammatory cell infiltration. In BAS nephritis, immune deposits were seen in mesangial, subendothelial, intramembranous and subepithelial areas. The deposits in the former three areas seemed to have little reciprocity with the loss of HS-PG and proteinuria. Urinary protein increased in accordance with the development of subepithelial deposits and the loss of HS-PG in the area of the deposits in the LRE. These results indicate that HS-PG could be preserved even in marked proteinuric states in morphologically intact basement membrane, but altered and lost distribution of HS-PG associated with subepithelial immune deposits could in turn result in the development of proteinuria.
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PMID:Altered glomerular localization of heparan sulfate proteoglycan in experimental nephritides. 294 56

Alterations of glomerular basement membrane (GBM) anionic (charge sites, CSs) in the development of proteinuria in a model of idiopathic nephrotic syndrome in man (puromycin aminonucleoside nephrotic syndrome [PAN] in the rat) were assessed quantitatively and sequentially early after disease induction. GBM CSs (known to consist mainly of heparan sulfate-rich proteoglycans) were stained in vivo and, in a separate group of animals by an in vitro method, with the cationic marker polyethyleneimine (PEI) studied by electron microscopic examination. Four hours after administration of PAN, there was a significant decrease in GBM lamina rara externa CSs: 18 +/- 0.7 versus 22.0 +/- 2.2 per 1000 nm GBM in controls by PEI injection and 17.2 +/- 2.7 versus 21.1 +/- 1.6 per 1000 nm GBM in controls by PEI in vitro staining. This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours). These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function.
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PMID:Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis. 378 94

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

The present study was designed to assess whether a specific endothelin A (ETA) receptor antagonist, FR139317, affects the progression of lupus nephritis and affects transcription of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1, and accumulation of ECM proteins in the renal cortex of NZB/W F1 mice. mRNA levels for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-1, -2, -3, and TIMP-1 increased significantly as nephritis progressed in NZB/W F1 mice. At 48 weeks of age, the levels of mRNA for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, HSPG, MMP-1, -2, -3, and TIMP-1 were increased by 5.6- (P < 0.001), 3.6- (P < 0.01), 6.8- (P < 0.001), 5.2- (P < 0.001), 5.0- (P < 0.001), 6.0- (P < 0.001), 7.6- (P < 0.001), 4.2- (P < 0.01), 8.2- (P < 0.001), and 15.2-fold (P < 0.001), respectively, in the renal cortex of NZB/W F1 mice compared to NZW mice. Immunofluorescence microscopy showed that the accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice increased markedly with the progression of nephritis. At 20 weeks of age, NZB/W F1 and NZW mice were divided into two groups that received either FR139317 or its vehicle (saline) intraperitoneally, daily, for 28 weeks. The development of histological lesions, proteinuria, hypertension, accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice were suppressed by FR139317 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a specific endothelin A receptor antagonist on murine lupus nephritis. 772 34

In recent years more than 150 cases of glomerulonephritis characterized by deposits of irregularly arranged fibrils have been documented. In the majority of these cases immunoglobulins and complement are the prime constituents of these deposits. We recently made a diagnosis of fibrillary glomerulonephritis without immunoglobulin deposition in two members of a family, a father and a son. In the father, proteinuria was first discovered 18 years ago. In 1985 he was referred to our outpatient clinic because of hypertension and increasing proteinuria. From that time onward he was regularly seen for blood pressure control. Nephrotic-range proteinuria persisted, without hardly any evidence of deterioration of renal function. Renal biopsies were performed in 1985 and 1993. His son underwent a renal biopsy in 1993 because of moderate proteinuria. The biopsies of both patients disclosed a distinct form of fibrillary glomerulonephritis that was characterized by massive deposits of a homogeneous, eosinophilic material in the mesangial and subendothelial areas. Staining for amyloid was negative. Immunofluorescence revealed that the biopsy specimens only stained faintly for immunoglobulins, complement factors C1q and C3, the extracellular matrix proteins, collagen IV, and laminin. However, they strongly stained for fibronectin. Using monoclonal antibodies specific for cell-derived fibronectin (IST-9) and plasma- and cell-derived fibronectin (IST-4), in the biopsy of the son we demonstrated that the fibronectin deposited in the glomeruli was mainly derived from the plasma, and to a lesser extent from resident glomerular cells. In addition, a moderate staining for amyloid P and vitronectin also was present. No or minor enhanced staining for collagen I, III, or V, heparan sulfate proteoglycan or its glycosaminoglycan side chains, tenascin, or thrombospondin could be observed. By electron microscopy the deposits in the mesangium and the subendothelial spaces appeared focally to be composed of irregularly arranged fibrils or microtubules 10 to 12 nm in diameter. Fibrillary glomerulonephritis with massive deposits of fibronectin represents a rare form of familial glomerulonephritis. In our patients the glomerulonephritis has an indolent course with hardly any deterioration of renal function.
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PMID:Familial glomerulonephritis characterized by massive deposits of fibronectin. 774 33

This study was designed to assess how the expression of genes for components of the extracellular matrix is altered in a model of focal glomerular sclerosis. In this model, a unilateral nephrectomy combined with injections of puromycin aminonucleoside induces a much higher incidence of focal glomerular sclerosis. Rats received puromycin aminonucleoside on days 0, 27, 34, and 41 and underwent unilateral nephrectomy on day 22. Control rats received physiologic saline injections with and without unilateral nephrectomy. Rats from each group were killed on days 48, 60, and 80. The steady-state levels of glomerular mRNA encoding type IV collagen, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, and type I and type III collagens were compared in both the puromycin aminonucleoside-treated and the control glomeruli. The mRNA levels encoding type IV collagen and laminin B1 and B2 were increased three-, two-, and twofold, respectively, on day 48 of focal glomerular sclerosis. These transcripts were further increased eight-, seven-, and eightfold, respectively, on day 80 compared with the control glomeruli (P < 0.01). In contrast, heparan sulfate proteoglycan mRNA levels were not increased on day 48 when the animals had marked proteinuria. However, the heparan sulfate proteoglycan mRNA levels did become elevated by day 60 and remained elevated thereafter. The expression of type I and type III collagen mRNA was increased 12- and 7-fold, respectively (P < 0.01), on day 80 in focal glomerular sclerosis rats compared with the controls. An immunofluorescence study revealed the accumulation of immunoglobulin M, C3, type IV collagen, laminin, heparan sulfate proteoglycan, and type I and type III collagens in the sclerotic area. These data indicate that changes in the mRNA levels for components of the basement membrane and interstitial collagen are associated with the development of glomerular sclerosis.
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PMID:Extracellular matrix component mRNA expression in glomeruli in experimental focal glomerulosclerosis. 843 50

Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capillaries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra- and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focus on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucose-induced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of extracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level.
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PMID:Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy. 851 35


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