Regulation of multiple renin-angiotensin system genes by Sry.

Regulation of multiple renin-angiotensin system genes by Sry.
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Sry 对多个肾素-血管紧张素系统基因的调节。

DOI:
10.1097/hjh.0b013e328332b88d
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发表时间:
2010
影响因子:
4.9
通讯作者:
Turner,MonteE
Turner,MonteE
中科院分区:
医学2区
文献类型:
--
作者:
Milsted,Amy;Underwood,AdamC;Dunmire,Jeff;DelPuerto,HelenL;Martins,AlmirS;Ely,DanielL;Turner,MonteE

文献摘要

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方法将含有血管紧张素原启动子(AGT−14 30/+2 2)、肾素(Ren−10 5 0/−1)、血管紧张素转换酶(ACE2−16 77/+2 1)和血管紧张素转换酶2(ACE2−10 91/+83)启动子的荧光素酶报告基因共转染CHO细胞。Sry3的作用最大,使血管紧张素原启动子活性增加1.7倍,肾素启动子活性增加1.3倍,ACE启动子活性增加2.6倍,ACE2启动子活性降低0.5倍。Sry1对启动子活性的影响明显小于Sry3。Sry2激活启动子的水平明显低于Sry1。Sry对肾素-血管紧张素系统中多个基因的调节作用或单个基因表达的改变可能导致Ang II水平升高,Ang-(1-7)水平降低。结论Sry的这些作用可导致男性血压升高,并导致血压性别差异。
MethodSry expression vectors were co-transfected into CHO cells with luciferase reporter constructs containing promoters of angiotensinogen (Agt− 1430/+ 22), renin (Ren− 1050/− 1), angiotensin-converting enzyme (ACE)(ACE− 1677/+ 21) and ACE2 (ACE2− 1091/+ 83).ResultsSry1, Sry2 and Sry3 differentially upregulated activity of the promoters of angiotensinogen, renin and ACE genes and downregulated ACE2 promoter activity. The largest effect was seen with Sry3, which increased activity of angiotensinogen promoter by 1.7-fold, renin promoter by 1.3-fold, ACE promoter by 2.6-fold and decreased activity of ACE2 promoter by 0.5-fold. The effect of Sry1 on promoter activity was significantly less than that of Sry3. Sry2 activated promoters at a significantly lower level than Sry1 did. The result of either an additive effect of Sry regulation of multiple genes in the renin–angiotensin system or alterations in expression of a single gene could favor increased levels of Ang II and decreased levels of Ang-(1-7).ConclusionThese actions of Sry could result in increased blood pressure in males and contribute to sex differences in blood pressure.