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)

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.
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PMID:Apoptosis in the kidneys of patients with type II diabetic nephropathy. 1862

Apoptotic cell death contributes to diabetic nephropathy (DN), but its role is not well understood. The tubulointerstitium from DN biopsy specimens was microdissected, and expression profiles of genes related to apoptosis were analyzed. A total of 112 (25%) of 455 cell death-related genes were found to be significantly differentially regulated. Among those that showed the greatest changes in regulation were two death receptors, OPG (the gene encoding osteoprotegerin) and Fas, and the death ligand TRAIL. Glomerular and proximal tubular TRAIL expression, assessed by immunohistochemistry, was higher in DN kidneys than controls and was associated with clinical and histologic severity of disease. In vitro, proinflammatory cytokines but not glucose alone regulated TRAIL expression in the human proximal tubular cell line HK-2. TRAIL induced tubular cell apoptosis in a dosage-dependant manner, an effect that was more marked in the presence of high levels of glucose and proinflammatory cytokines. TRAIL also activated NF-kappaB, and inhibition of NF-kappaB sensitized cells to TRAIL-induced apoptosis. It is proposed that TRAIL-induced cell death could play an important role in the progression of human DN.
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PMID:The death ligand TRAIL in diabetic nephropathy. 1828 63

Cell death is thought to contribute to progressive renal cell depletion in diabetic nephropathy. Unbiased gene expression profiling identified novel cell death molecules in human diabetic nephropathy. The expression of TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin, and receptors Fas (a Fas ligand receptor) and CD74 (a migration inhibitory factor (MIF) receptor) were induced in human diabetic nephropathy. Cell culture studies supported the functional relevance of this observation and the relationship to a high glucose environment. To define novel proapoptotic proteins upregulated in diabetic nephropathy, functional genomic screens for novel apoptosis mediators were integrated with genome-wide expression profiling and identified candidates for further functional analysis, including brain acid-soluble protein 1 (BASP1). Several lines of evidence point toward induction of endoplasmic reticulum stress response in human diabetic nephropathy. Functional studies defining an unequivocal contribution of endoplasmic reticulum stress to cell death in this setting are still needed. Further comparative studies will be required to define whether there is a specific aspect of apoptosis in progressive human diabetic nephropathy or whether the mechanisms are shared among all patients with chronic kidney disease. The next challenge will be to define the consequence of therapeutic interference of the apoptosis pathways in diabetic nephropathy and chronic kidney disease.
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PMID:New paradigms in cell death in human diabetic nephropathy. 2070 12

Objective To investigate the expression of apoptosis-related factors in diabetic nephropathy model rats after the intervention of dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. Methods ZDF(fa/fa) and ZDF(fa/+) rats were randomly divided into diabetes mellitus group and sitagliptin treatment group, and ZDF control mice (fa/+) were used as the control group. Non-fasting blood glucose levels were measured with glucose oxidase kit. Urine albumin level was detected by ELISA, and blood biochemical indexes were detected by automatic biochemical analyzer. The mRNA levels of tumor necrosis factor receptor 1(TNFR1), Fas, and caspase-3 in the renal tissue were examined by real-time fluorescence quantitative PCR, and the protein levels of DPP-4, GLP-1, TNFR1, caspase-3, and caspase-8 were detected by Western blot analysis. Results The levels of blood glucose, urinary microalbumin, blood urea nitrogen, serum creatinine increased in the diabetic group, and the levels of related indicators significantly decreased after treatment with sitagliptin. The mRNA levels of TNFR1 and caspase-3 in the diabetic rats went up and then down after the treatment with sitagliptin. The levels of DPP-4, TNFR1, caspase-3 and caspase-8 in the diabetic rats increased, while the level of GLP-1 decreased; after the treatment with sitagliptin, the corresponding protein content showed opposite changes. Conclusion Sitagliptin can inhibit inflammation and apoptosis in rats with diabetic nephropathy.
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PMID:[Sitagliptin inhibits cell apoptosis and inflammation of renal tissues in diabetic nephropathy model rats]. 3103 Jul 14