Hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice
Hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice
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DOI：
10.1152/ajplung.1997.273.4.l848
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发表时间：
1997-10-01
影响因子：
4.9
通讯作者：
Webb, ML
中科院分区：
文献类型：
--
作者：
Aversa, CR;Oparil, S;Webb, ML
内皮素（ET）-1水平的显著升高伴随许多疾病，但其潜在的调节机制尚不清楚。为了研究人前内皮素原-1（PPET-1）的体内调节，我们检测了暴露于缺氧的转基因小鼠中PPET-1启动子的活性。产生表达三种PPET-1启动子-荧光素酶（PPET-1/LUC）报告转基因（约2.5kb，138 bp，或没有PPET-1基因的5 ′-侧翼序列）之一的小鼠。LUC的表达减少在小鼠与截短的138 bp的PPET-1启动子。暴露小鼠轴承2.5 kb PPET-1/LUC转基因缺氧（10%O-2 24小时）增加LUC表达在肺组织中的6倍，但在其他组织中只有2倍。原位杂交显示，最强的转基因表达在肺血管和细支气管上皮。这些数据与PPET-1基因的低氧诱导导致与低O-2张力相关的疾病中ET-1的肺产生增加的假设一致。
Significant elevations in endothelin (ET)-1 levels accompany many diseases, but the underlying regulatory mechanisms are unclear. To investigate the in vivo regulation of human preproendothelin-1 (PPET-1), we examined the activity of the PPET-1 promoter in transgenic mice exposed to hypoxia. Mice expressing one of three PPET-1 promoter-luciferase (PPET-1/LUC) reporter transgenes (approximate to 2.5 kb, 138 bp, or none of the 5'-flanking sequences of the PPET-1 gene) were generated. LUC expression was reduced in mice with a truncated 138-bp PPET-1 promoter. Exposure of mice bearing the 2.5-kb PPET-1/LUC transgene to hypoxia (10% O-2 for 24 h) increased LUC expression sixfold in pulmonary tissue but only twofold in other tissues. In situ hybridization revealed the strongest transgene expression in the pulmonary vasculature and bronchiolar epithelium. These data are consistent with the hypothesis that hypoxic induction of the PPET-1 gene leads to increased pulmonary production of ET-1 in diseases associated with low O-2 tension.