Role of upstream stimulatory factor 2 in diabetic nephropathy.
Role of upstream stimulatory factor 2 in diabetic nephropathy.
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DOI：
10.1007/s11515-015-1359-x
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发表时间：
2015-06
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影响因子：
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通讯作者：
Wang S
中科院分区：
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作者：
Wang S
糖尿病肾病(DN)是终末期肾病(ESRD)最常见的病因。大约20%-30%的1型和2型糖尿病患者会发展为DN。肾小球硬化伴肾小球基底膜增厚和系膜基质扩张，以及肾小管间质纤维化。糖尿病患者的高血糖和肾内肾素-血管紧张素系统（RAS）的激活被认为在DN的发病机制中起关键作用。然而，其机制尚不清楚。我们实验室的研究表明转录因子-上游刺激因子2 （USF2）是DN的重要调节因子。此外，肾素基因是USF2的下游靶点。重要的是，USF2转基因（Tg）小鼠表现出肾脏肾素表达和血管紧张素II （AngII）水平的特异性增加，尿白蛋白排泄和肾小球细胞外基质沉积增加，支持USF2在糖尿病肾病发展中的作用。在这篇综述中，我们总结了糖尿病调节肾细胞中USF2的机制及其在调节肾素-血管紧张素系统和糖尿病肾病发生中的作用。
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.