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 podocyte is the cell responsible in large part for maintaining the glomerular filtration barrier. Glomerular epithelial protein 1 (GLEPP1) is a novel receptor-like transmembrane protein tyrosine phosphatase present on the apical surface of podocyte foot processes. Podocalyxin-like protein 1 (PCLP1) is a transmembrane sialoglycoprotein which is also present on the foot process apical surface as well as on the surface of endothelial cells. GLEPP1 and PCLP1 are thought to play a role in regulating the structure and function of podocyte foot processes. Glomerular injury affecting the podocyte is likely to be reflected by changes in these proteins. GLEPP1 distribution in human renal biopsy with inflammatory glomerular disease and crescent formation was examined by immunocytochemistry. A model of inflammatory glomerular injury induced by guinea pig anti-rabbit basement membrane (anti-GBM) antibody was used to examine the distribution and amount of GLEPP1 and PCLP1 mRNA and protein. A biopsy study was done to determine whether the extent of GLEPP1 depletion from glomeruli at early time points (Day 7) would predict the severity of crescent formation at Day 30. Glomeruli from human renal biopsies with crescentic nephritis showed focal to diffuse disappearance of GLEPP1 protein. No GLEPP1 was present within the cellular crescent. By Day 4 of the rabbit anti-GBM model, before cellular crescents had formed, GLEPP1 protein was reduced from 127 +/- 28 X 10(7) to 30 +/- 5 X 10(7) molecules per glomerulus (p < 0.001), and GLEPP1 mRNA was reduced by 62% (p < 0.05). In contrast, at this time there was no significant reduction of PCLP1 protein from the normal number of 309 X 10(9) molecules per glomerulus and the PCLP1 mRNA level had not decreased. At Day 4, podocyte foot processes were effaced and proteinuria was present. Glomerular culture supernatants from Day 4 rabbits caused a reduction in GLEPP1 but not PCLP1 protein expression by cultured normal glomeruli, showing that a soluble factor was produced at Day 4 which reduced the number of GLEPP1 molecules in glomeruli. There was no detectable proteolysis of GLEPP1 or PCLP1 in glomeruli and no increase in GLEPP1 or PCLP1 excretion in urine. Therefore, the reduction in glomerular GLEPP1 was associated with reduced synthetic capacity. The proportion of glomeruli with reduced GLEPP1 at Day 7 of the model was significantly associated with the percent of glomeruli which had formed crescents at Day 30 (r = 0.86, p < 0.0001). GLEPP1 appears to be a sensitive indicator of glomerular injury during inflammation in man and in the rabbit model. A reduction in amount of GLEPP1 is associated with worse outcome for the glomerulus.
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PMID:Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man. 860 Mar 7

Nitric oxide (NO) has been implicated in the induction of proteinuria in acute inflammatory glomerulonephritis and in the increased vascular permeability seen in various other disease conditions. The complicated interactions of NO with other factors in vivo hinder analysis of the mechanisms involved. By use of a recently introduced method for measuring albumin permeability (P(a)) in isolated glomeruli, the question of whether NO has a direct effect on the permeability barrier of glomerular tufts was examined and the potential mechanisms were explored. Exposure of isolated glomeruli to three NO donors, s-nitroso-N-acetyl-penicillamine (SNAP), (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), and sodium nitroprusside, all increased the P(a). This action of NO was time- and concentration-dependent and could be mimicked by 8-bromoguanosine 3', 5'-cyclic monophosphate. Western blot analysis of the proteins from NO donor-treated glomeruli revealed an increase of phosphotyrosine levels of proteins of molecular mass about 120 and 70 kD. The demonstration that pretreatment of glomeruli with the tyrosine kinase inhibitor, genistein, could largely prevent the effect of SNAP and DETA-NONOate confirmed the crucial role of tyrosine phosphorylation in the NO-induced increase of P(a). Furthermore, the tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), could mimic the action of NO on P(a). NO-enhanced tyrosine phosphorylation was further confirmed by immunofluorescence staining, where positive cells in SNAP- and PAO-treated glomeruli were much more frequent than that in controls. By use of dual-label staining in combination with podocyte specific marker, nephrin, it was observed that most of the phosphorylated positive cells corresponded to podocytes. These results suggest that NO impairs the glomerular permeability barrier through a tyrosine phosphorylation-dependent mechanism.
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PMID:Nitric oxide increases albumin permeability of isolated rat glomeruli via a phosphorylation-dependent mechanism. 1172 30

Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.
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PMID:GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury. 1196 7

The NEPH family comprises three transmembrane proteins of the Ig superfamily interacting with the glomerular slit diaphragm proteins podocin and ZO-1. NEPH1 binds to nephrin, another component of the slit diaphragm, and loss of either partner causes heavy proteinuria. NEPH2, which is strongly conserved among a large number of species, is also expressed in the kidney; however, its function is unknown. The authors raised NEPH2 antisera to demonstrate NEPH2 expression in a variety of mouse tissues, including the kidney and a podocyte cell line. The authors localized the expression of NEPH2 to the glomerular slit diaphragm by electron microscopy and show NEPH2 homodimerization and specific interactions with the extracellular domain of nephrin in vitro and in vivo. NEPH1, however, failed to interact with NEPH2. The authors detected immunoreactive NEPH2 in urine of healthy subjects, suggesting that the extracellular domain is cleaved under physiologic conditions. These findings were confirmed in vitro in podocyte cell culture. Shedding is increased by tyrosine phosphatase inhibitors and diminished by GM6001, an inhibitor of metalloproteinases. Overexpression experiments indicate an involvement of the MT1-matrix metalloproteinase. The results suggest a role for NEPH2 in the organization and/or maintenance of the glomerular slit diaphragm that may differ from the functions of NEPH1 and nephrin.
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PMID:NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases. 1584 75

Expression of glomerular epithelial protein 1 (GLEPP1), a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte, and podocyte morphology were investigated in renal specimens from 51 patients with biopsy-diagnosed immunoglobulin A nephropathy (IgAN) and 11 controls. Clinical parameters, such as daily proteinuria were obtained from the patients' records and pathological manifestations of IgAN in the specimens were graded. GLEPP1 was strongly expressed and diffusely distributed in the glomeruli of control specimens. GLEPP1 expression was reduced in IgAN, especially in patients with nephrotic proteinuria and severe pathological manifestations. Podocyte injury was evident in IgAN and was associated with lower GLEPP1 expression and higher pathological grade. GLEPP1 expression was also significantly associated with clinical parameters. The results of this study suggest that GLEPP1 expression may be a useful marker of podocyte injury in IgAN, and may be predictive of clinical and pathological severity.
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PMID:Reduced glomerular epithelial protein 1 expression and podocyte injury in immunoglobulin A nephropathy. 1759 62