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 expression of the protein products and mRNA of c-fos, c-myc, p53, and c-raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c-fos and c-myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.
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PMID:Proto-oncogene expression in human glomerular diseases. 877 42

Growth and injury represent recurrent and related themes in the study of progressive renal disease. We have previously demonstrated that a prooxidant diet, one deficient in antioxidants, selenium and vitamin E, induces renal enlargement, proteinuria, mild tubulointerstitial disease and diminished glomerular filtration rate (GFR). Our present study represents continued examination of these processes. We demonstrate that these diets increase thymidine incorporation into DNA and net DNA content in renal tissue, and induce expression of the mRNA for the proto-oncogene, c-myc, and the histone, H2b. We localize increased DNA synthesis as occurring mainly in the distal renal tubular epithelium. These deficient kidneys also exhibit interstitial expansion that parallels the pattern of DNA synthesis in that both processes are more prominent in the medulla than in the cortex. mRNAs for collagens I, III and IV in conjunction with transforming growth factor-beta1 (TGF-beta1) are up-regulated in the kidney in rats maintained on the deficient diet. In complementary in vitro studies, the exposure of rat kidney fibroblasts, NRK 49F cells, to noncytolytic doses of hydrogen peroxide, induces collagen III, collagen IV and TGF-beta1 mRNA. Induction of these genes is also observed in mesangial cells so exposed to noncytolytic doses of hydrogen peroxide. A final aspect of our study was the examination of renal generation of hydrogen peroxide and the profile of the hydrogen peroxide-degrading enzymes. Deficient kidneys exhibit increased mitochondrial generation of hydrogen peroxide independent of oxygen consumption but in conjunction with suppression of glutathione peroxidase mRNA and activity. Lipid peroxidation was increased twofold in the cortex and medulla of the deficient kidneys. Surprisingly, catalase activity, measured in the cortex and medulla, and whole kidney catalase mRNA were also reduced in rats maintained on the antioxidant deficient diet, effects that may further compromise the clearance of hydrogen peroxide. These changes in catalase represent an adverse response to this dietary deficiency, and may be relevant to decreased catalase activity described in chronic renal insufficiency. Thus, a chronic prooxidant state, with features that mimic those of clinical uremia, increases DNA synthesis of renal tubular epithelium, induces mRNA expression for collagens I, III and IV in conjunction with the mRNA for the fibrogenic cytokine, TGF-beta1. Oxidants also induce collagen III, collagen IV and TGF-beta1 mRNA in vitro.
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PMID:Redox regulation of renal DNA synthesis, transforming growth factor-beta1 and collagen gene expression. 946 Oct 96

We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.
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PMID:Effects of lisinopril administration on blood bcl-2 concentrations in patients with immunoglobulin A nephropathy. 1039 70

Several lines of evidence, including familial aggregation, suggest that allelic variation contributes to risk of diabetic nephropathy. To assess the evidence for specific susceptibility genes, we used the transmission/disequilibrium test (TDT) to analyze 115 candidate genes for linkage and association with diabetic nephropathy. A comprehensive survey of this sort has not been undertaken before. Single nucleotide polymorphisms and simple tandem repeat polymorphisms located within 10 kb of the candidate genes were genotyped in a total of 72 type 1 diabetic families of European descent. All families had at least one offspring with diabetes and end-stage renal disease or proteinuria. As a consequence of the large number of statistical tests and modest P values, findings for some genes may be false-positives. Furthermore, the small sample size resulted in limited power, so the effects of some tested genes may not be detectable, even if they contribute to susceptibility. Nevertheless, nominally significant TDT results (P < 0.05) were obtained with polymorphisms in 20 genes, including 12 that have not been studied previously: aquaporin 1; B-cell leukemia/lymphoma 2 (bcl-2) proto-oncogene; catalase; glutathione peroxidase 1; IGF1; laminin alpha 4; laminin, gamma 1; SMAD, mothers against DPP homolog 3; transforming growth factor, beta receptor II; transforming growth factor, beta receptor III; tissue inhibitor of metalloproteinase 3; and upstream transcription factor 1. In addition, our results provide modest support for a number of candidate genes previously studied by others.
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PMID:Assessment of 115 candidate genes for diabetic nephropathy by transmission/disequilibrium test. 1624 59

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.
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PMID:Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. 1662 51