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)

Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.
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PMID:Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy. 138 96

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