The regulation of the induction of vascular endothelial growth factor at the onset of diabetes in spontaneously diabetic rats

The regulation of the induction of vascular endothelial growth factor at the onset of diabetes in spontaneously diabetic rats
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DOI:
10.1016/s0024-3205(01)01327-3
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发表时间:
2001-10-12
期刊:
影响因子:
6.1
通讯作者:
Mandl, J
Mandl, J
中科院分区:
医学2区
文献类型:
--
作者:
Braun, L;Kardon, T;Mandl, J

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研究自发性糖尿病大鼠肝、肾和肺中VEGF的早期诱导。Western blot分析、北方杂交检测VEGF在不同器官中的表达。用抗ARNT和抗CREB-1单克隆抗体,通过电泳迁移率变动(EMSA)或超迁移率变动(supershift)分析放射性标记的缺氧反应元件(HRE)和cAMP反应元件(CRE)寡核苷酸。VEGF在蛋白质和mRNA水平上的表达在疾病开始时增加。EMSA显示:a.)a HIF-1与HRE和/或CRE的结合,B.)同时,在糖尿病动物的肝、肾和肺中检测到CREB-1与HRE和/或CRE序列的结合。基于这些体内观察,推测HRE和CRE通过HIF-1和CREB-1之间的相互作用同等地参与糖尿病发作时VEGF表达的调节。(C)2001 Elsevier Science Inc. All rights reserved.
Early induction of VEGF was studied in liver, kidney and lung of spontaneously diabetic rats. Western blot analysis, northern hybridization were applied to show the expression of VEGF in different organs. Radiolabelled hypoxia responsive element (HRE) and cAMP responsive element (CRE) oligonucleotides were assayed by electrophoretic mobility shift (EMSA) or supershift using anti ARNT and anti CREB-1 monoclonal antibodies. An increase in VEGF expression at the level of protein and mRNA was demonstrated at the beginning of the disease. EMSAs showed: a.) a binding of HIF-1 to HRE and/or CRE, b.) in the same time the binding of CREB-1 was detected to both HRE and/or CRE sequences in the liver, kidney and lung of diabetic animals. Based on these in vivo observations it is supposed that HRE and CRE through the interaction between HIF-1 and CREB-1 are equally involved in the regulation of VEGF expression at the onset of diabetes. (C) 2001 Elsevier Science Inc. All rights reserved.