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)

Mesangial cells are responsible for the synthesis of mesangial matrix as well as its degradation, which is mediated by a number of proteolytic activities, including metalloproteinases (MMPs). Imbalanced matrix protein metabolism may be responsible for mesangial expansion and glomerulosclerosis in diabetic nephropathy. Heparin prevents this complication. In human and murine mesangial cell cultures, RT-PCR was able to detect mRNA expression for a number of molecules involved in the mesangial extracellular matrix turnover: type IV collagen [alpha 1(IV)COLL], MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10, and the tissue inhibitors TIMP-1 and TIMP-2. The expression of mRNA for alpha 1(IV)COLL and MMP-2/TIMP-2 balance was studied in human cells in the presence of high glucose and heparin. mRNAs for all the studied molecules were expressed at different levels. Interestingly, a shift in the balance of alpha 1(IV)COLL, MMP-2 and TIMP-2 was observed in high glucose, which was partially reversed by heparin supplementation. The new equilibrium was mostly due to the down-regulation of type IV collagen expression, rather than further reduction of potential proteolysis. Our data, while extending the list of potential mediators of mesangial matrix catabolism, highlight a molecular mechanism by which the pathogenesis of diabetic nephropathy may be sustained, and at the same time suggest that heparin may have the potential to correct this abnormality.
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PMID:Effect of glucose and heparin on mesangial alpha 1(IV)COLL and MMP-2/TIMP-2 mRNA expression. 907 22

Diabetic nephropathy (DN) is a common complication of diabetes types 1 and 2. One of the hallmarks of DN is the development of mesangial expansion, which occurs through accumulation of extracellular matrix (ECM) components. Altered local gene expression of humoral factors (eg, transforming growth factor-b, connective tissue growth factor, and platelet-derived growth factor) can lead to increased production of ECM components (eg, fibronectin and collagen IV) or decreased degradation through matrix metalloproteinases (eg, MMP-1, MMP-2). In recent years, new techniques for examination of gene expression have been developed. Because of their large scale and high-throughput character, it is now possible to examine differential gene expression in a large number of samples. This paper provides an overview of techniques used and results obtained in studies of DN. Newly developed concepts of how altered gene expression may affect histomorphologic features or clinical symptoms are also discussed.
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PMID:Gene expression in diabetic nephropathy. 1553 12

Type 2 Diabetic Nephropathy (DN) is a common multifactorial disorder. Degradation of glomerular basement membrane (GBM) by matrix metalloproteases (MMPs) is a key event in the progression of renal disease. A functional polymorphism at position -1607 1G/2G, -1306 C/T and -1171 5A/6A has been shown to alter the transcriptional activity of MMP-1, MMP-2, and MMP-3 respectively, and also associated with several diseases contributing to inter-individual differences in susceptibility to type 2 DN. The study population consisted of 310 type 2 DN patients and 310 healthy controls. Genotypes of MMP-1, 2 and 3 were determined by PCR-RFLP assay. Gene interactions, Linkage disequilibrium, and haplotype analysis were carried out by MDR analysis and Haploview software respectively. The promoter binding sites of MMP genes were determined by using Alibaba 2.1 and the gene-gene interactions of MMPs were analyzed by GeneMania. The individuals carrying 2G allele of -1607, C allele of -1306 and 5A/6A genotype of -1171 were associated with type 2 DN susceptibility and progression from stage 1 to stage 5. 2G-5A haplotypes of MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) gene polymorphisms were found to be significantly predominant in the disease group. MDR analysis revealed a strong interaction between the genes under study. 2G allele of MMP-1, C allele of MMP-2 and 5A/6A genotype of MMP-3 were associated with susceptibility and disease progression of type 2 DN and might be used as potential markers for risk prediction and prognosis of type 2 DN.
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PMID:Collagenase-1 (-1607 1G/2G), Gelatinase-A (-1306 C/T), Stromelysin-1 (-1171 5A/6A) functional promoter polymorphisms in risk prediction of type 2 diabetic nephropathy. 2988 60