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)

It is generally considered that genetic factors may contribute to the susceptibility of type 2 diabetic nephropathy. The purpose of the present study is to identify molecules that contribute to the development and/or progression of this disease. Differential display was performed to isolate genes in the kidney using the KK/Ta mouse model of type 2 diabetes. The differential expression of 8 randomly chosen candidate genes (DN1-8) were verified by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis. DN1-3 (Zn-alpha2-glycoprotein, vascular endothelial growth factor receptor [VEGFR]-2, and lactate dehydrogenase [LDH]) were overexpressed and DN7-8 (peroxisome proliferator-activated receptor [PPAR]-interacting protein [PRIP], unknown) were underexpressed in the KK/Ta mouse kidney. DN4-6 (Ezrin, transcobalamin 2, aldo-ketoreductase) did not differ between KK/Ta and control (BALB/c) mice. DN8 only showed no significant sequence similarity to previously reported genes. Molecular cloning revealed that full-length DN8 shares 89% identity with human cholinephosphotransferase 1 (hCHPT1), and we designated it as "putative" mouse cholinephosphotransferase 1 (mCHPT1). The putative mCHPT1 gene was most closely mapped to the D10Mit94 locus with the highest logarithm of odds (lod) score. In situ hybridization revealed the levels of glomerular putative mCHPT1 in BALB/c mice tended to be slightly higher than those in KK/Ta mice. The altered renal mRNA expression of these genes may be involved in the development and/or progression of diabetic nephropathy.
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PMID:Altered mouse cholinephosphotransferase gene expression in kidneys of type 2 diabetic KK/TA mouse. 1525 74

Tissue kallikrein is the main kinin-forming enzyme in mammals, and differences in kinin levels are thought to be a contributing factor to diabetic nephropathy. Here, we determined the role of the kallikrein-kinin system in the pathogenesis of streptozotocin-induced diabetic nephropathy in wild-type and tissue kallikrein-knockout mice. All diabetic mice developed similar hyperglycemia, but the knockout mice had a significant two-fold increase in albuminuria compared to the wild-type mice before and after blood pressure elevation. Ezrin mRNA, a podocyte protein potentially implicated in albuminuria, was downregulated in the kidney of knockout mice. One month after induction of diabetes, the mRNAs of kininogen, tissue kallikrein, kinin B1, and B2 receptors were all increased up to two-fold in the kidney in both genotypes. Diabetes caused a 50% decrease in renal angiotensin-converting enzyme expression and a 20-fold increase in kidney injury molecule-1 reflecting tubular dysfunction, but there was no genotype difference. Our study found an early activation of the kallikrein-kinin system in the kidney and that this has a protective role against the development of diabetic nephropathy. The effect of tissue kallikrein deficiency on microalbuminuria in diabetic mice is similar to the effect of genetically high angiotensin-converting enzyme levels, suggesting that both observations, in part, result from a deficiency in kinins.
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PMID:Kallikrein protects against microalbuminuria in experimental type I diabetes. 1951 48

Diabetic nephropathy is a complication of diabetes and a major cause of end-stage renal disease. To characterize the early pathophysiological mechanisms leading to glomerular podocyte injury in diabetic nephropathy, we performed quantitative proteomic profiling of glomeruli isolated from rats with streptozotocin-induced diabetes and controls. Fluorescence-based two-dimensional difference gel electrophoresis, coupled with mass spectrometry, identified 29 differentially expressed spots, including actin-binding protein ezrin and its interaction partner, NHERF2, which were down-regulated in the streptozotocin group. Knockdown of ezrin by siRNA in cultured podocytes increased glucose uptake compared with control siRNA-transfected cells, apparently by increasing translocation of glucose transporter GLUT1 to the plasma membrane. Knockdown of ezrin also induced actin remodeling under basal conditions, but reduced insulin-stimulated actin reorganization. Ezrin-dependent actin remodeling involved cofilin-1 that is essential for the turnover and reorganization of actin filaments. Phosphorylated, inactive cofilin-1 was up-regulated in diabetic glomeruli, suggesting altered actin dynamics. Furthermore, IHC analysis revealed reduced expression of ezrin in the podocytes of patients with diabetes. Our findings suggest that ezrin may play a role in the development of the renal complication in diabetes by regulating transport of glucose and organization of the actin cytoskeleton in podocytes.
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PMID:Ezrin is down-regulated in diabetic kidney glomeruli and regulates actin reorganization and glucose uptake via GLUT1 in cultured podocytes. 2472 96