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)

Diabetic nephropathy is the most common cause of end-stage renal failure in the United States. Hyperglycemia is an important factor in the pathogenesis of diabetic nephropathy. Hyperglycemia upregulates the expression of transforming growth factor-beta (TGF-beta), which stimulates extracellular matrix deposition in the kidney, contributing to the development of diabetic nephropathy. Our previous studies demonstrated that the transcription factor, upstream stimulatory factor 2 (USF2), was upregulated by high glucose, which bound to an 18-bp sequence in the thrombospondin 1 (TSP1) gene promoter and regulated high glucose-induced TSP1 expression and TGF-beta activity in mesangial cells, suggesting that USF2 might play a role in the development of diabetic nephropathy. In the present studies, we examined the effect of overexpression of USF2 on the development of diabetic nephropathy. Type 1 diabetes was induced in USF2 transgenic mice [USF2 (Tg)] and their wild-type littermates (WT) by injection of streptozotocin. Four groups of mice were studied: control WT, control USF2 (Tg), diabetic WT, and diabetic USF2 (Tg). Mice were killed after 15 wk of diabetes onset. At the end of studies, control USF2 (Tg) mice ( approximately 6 mo old) exhibited increased urinary albumin excretion. These mice also exhibited glomerular hypertrophy, accompanied by increased TSP1, active TGF-beta, fibronectin accumulation in the glomeruli compared with control WT littermates. Type 1 diabetes onset further augmented the urinary albumin excretion and glomerular hypertrophy in the USF2 (Tg) mice. These findings suggest that overexpression of USF2 accelerates the development of diabetic nephropathy.
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PMID:Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury. 1788 61

Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. We previously demonstrated that a transcription factor called upstream stimulatory factor 2 (USF2) was upregulated in the kidneys from diabetic animals in vivo as well as in mesangial cells (MCs) exposed to high-glucose media in vitro. USF2 mediates glucose-induced thrombospondin 1 expression and transforming growth factor-beta activity in MCs and plays a role in DN. Glycated proteins have been shown to accumulate in the kidneys of diabetic patients and contribute to DN. However, whether glycated proteins regulate USF2 expression in MCs and play a role in DN is unknown. In the present studies, we determined the effect of glycated albumin on UFS2 gene expression in primary rat MCs. We found that glycated albumin upregulated USF2 expression (mRNA and protein) in a dose- and time-dependent manner. We also demonstrated that glycated albumin stimulated USF2 gene expression at the transcriptional level. By using the luciferase-promoter deletion assay, site-directed mutagenesis, and transactivation assay, we identified a glycated albumin-responsive region in the USF2 gene promoter (-837 to -430, relative to the transcription start site) and demonstrated that glycated albumin-induced USF2 expression was mediated through NF-kappaB-dependent transactivation of the USF2 promoter. Furthermore, glycated albumin increased nuclear NF-kappaB subunit-p65 protein levels. siRNA-mediated p65 knockdown prevented glycated albumin-induced USF2 gene expression (promoter activity, mRNA, and protein levels). Taken together, these data suggest that glycated albumin upregulated USF2 gene transcription in MCs through NF-kappaB-dependent transactivation of the USF2 promoter.
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PMID:Glycated albumin upregulates upstream stimulatory factor 2 gene transcription in mesangial cells. 2041 Feb 11

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). About 20%-30% of people with type 1 and type 2 diabetes develop DN. DN is characterized by both glomerulosclerosis with thickening of the glomerular basement membrane and mesangial matrix expansion, and tubulointerstitial fibrosis. Hyperglycemia and the activation of the intra-renal renin-angiotensin system (RAS) in diabetes have been suggested to play a critical role in the pathogenesis of DN. However, the mechanisms are not well known. Studies from our laboratory demonstrated that the transcription factor-upstream stimulatory factor 2 (USF2) is an important regulator of DN. Moreover, the renin gene is a downstream target of USF2. Importantly, USF2 transgenic (Tg) mice demonstrate a specific increase in renal renin expression and angiotensin II (AngII) levels in kidney and exhibit increased urinary albumin excretion and extracellular matrix deposition in glomeruli, supporting a role for USF2 in the development of diabetic nephropathy. In this review, we summarize our findings of the mechanisms by which diabetes regulates USF2 in kidney cells and its role in regulation of renal renin-angiotensin system and the development of diabetic nephropathy.
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PMID:Role of upstream stimulatory factor 2 in diabetic nephropathy. 2649 84