Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid-mediated injury plays an important role in the pathogenesis of many renal diseases including diabetic nephropathy. Liver X receptor-alpha (LXRalpha) is an intracellular sterol sensor that regulates expression of genes controlling cholesterol absorption, excretion, catabolism, and cellular efflux. The present study was aimed at examining the role of LXRalpha in cholesterol metabolism in glomerular mesangial cells. A 1,561-bp fragment of full-length rabbit LXR cDNA was cloned. The deduced protein sequence exhibited 92.4 and 89.2% identity to human and mouse LXRalpha, respectively. Tissue distribution studies showed that rabbit LXRalpha was expressed in the liver, spleen, and kidney. In situ hybridization and RT-PCR assays further indicated that LXRalpha mRNA was widely expressed in the kidney and present in every nephron segment including the glomeruli. To determine intrarenal regulation of LXRalpha, rabbits were treated with thiazolidinedione (TZD) peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, which have been previously shown to enhance LXRalpha expression via PPARgamma and increase cholesterol efflux in macrophages. The results showed that glomerular LXRalpha expression was markedly induced by TZDs. In cultured rabbit mesangial cells, LXRalpha mRNA and protein were detected by RT-PCR and immunoblotting. Treatment of mesangial cells with a specific LXRalpha agonist, TO-901317, significantly increased basal and apolipoprotein AI-mediated cholesterol efflux and markedly enhanced the promoter activity of an LXRalpha target gene, ATP-binding cassette transporter A1 (ABCA1). In conclusion, LXRalpha is expressed in renal glomeruli and functionally present in mesangial cells where its activation mediates cholesterol efflux via ABCA1. These data suggest that LXRalpha may be a potential therapeutic target for treating lipid-related renal glomerular disease.
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PMID:Liver X receptor-alpha mediates cholesterol efflux in glomerular mesangial cells. 1528 Jan 60

Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy.
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PMID:Proteome analysis of serum from type 2 diabetics with nephropathy. 1726 29

INTRODUCTION: As part of a clinical proteomics programme focused on diabetes and its complications, it was our goal to investigate the proteome of plasma in order to find improved candidate biomarkers to predict diabetic nephropathy. METHODS: Proteins derived from plasma from a cross-sectional cohort of 123 type 1 diabetic patients previously diagnosed as normoalbuminuric, microalbuminuric or macroalbuminuric were enriched with hexapeptide library beads and subsequently pooled within three groups. Proteins from the three groups were compared by online liquid chromatography and tandem mass spectrometry in three identical repetitions using isobaric mass tags (iTRAQ). The results were further analysed with ingenuity pathway analysis. Levels of apolipoprotein A1, A2, B, C3, E and J were analysed and validated by a multiplex immunoassay in 20 type 1 diabetic patients with macroalbuminuria and 10 with normoalbuminuria. RESULTS: A total of 112 proteins were identified in at least two out of three replicates. The global protein ratios were further evaluated by ingenuity pathway analysis, resulting in the recognition of apolipoprotein A2, B, C3, D and E as key nodes in the top-rated network. The multiplex immunoassay confirmed the overall protein expression patterns observed by the iTRAQ analysis. CONCLUSION: The candidate biomarkers discovered in this cross-sectional cohort may turn out to be progression biomarkers and might have several clinical applications in the treatment and monitoring of diabetic nephropathy; however, they need to be confirmed in a longitudinal cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9053-0) contains supplementary material, which is available to authorized users.
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PMID:Quantitative iTRAQ-Based Proteomic Identification of Candidate Biomarkers for Diabetic Nephropathy in Plasma of Type 1 Diabetic Patients. 2112 97

It is well known that patients with diabetes have a high incidence of cardiovascular disease (CVD), and the incidence of CVD becomes substantially elevated with development of diabetic nephropathy. The mechanisms for dyslipidemia in diabetic nephropathy are multifactorial and complex. Long-term hyperglycemia causes generalized vascular endothelial damage, which reduces functional lipoprotein lipase, leading to increased triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C). In overt-diabetic nephropathy, hypoproteinemia markedly increases low-density lipoprotein cholesterol (LDL-C), and renal failure specifically increases remnant lipoproteins and decreases HDL-C and LDL-C. Overt diabetic nephropathy exhibits remarkable postprandial hypertriglyceridemia with hyper-apolipoprotein (apo) B48, a marker of chylomicron and its remnants. Apo CIII is a key inhibitor of lipolysis and particle uptake of TG-rich lipoproteins, which is specifically increased in advanced chronic kidney disease, irrespective of the presence of diabetes. LDL size becomes smaller with advanced stages of diabetic nephropathy, whereas LDL size is not reduced in hemodialysis patients (HD). HD patients have marked lower levels of HDL3-C than controls. HD patients also have substantially low apo AI and high serum amyloid A (SAA) levels, suggesting the replacement of apo AI by SAA is stimulated in HDL particles.
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PMID:Abnormal lipoprotein metabolism in diabetic nephropathy. 2413 62


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