Maternal protein restriction induces renal AT2R promoter hypomethylation in salt-sensitive, hypertensive rats.
Maternal protein restriction induces renal AT2R promoter hypomethylation in salt-sensitive, hypertensive rats.
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母体蛋白限制导致盐敏感高血压大鼠肾脏AT2R启动子低甲基化。
DOI：
10.1002/fsn3.2113
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发表时间：
2021-03
影响因子：
3.9
通讯作者：
Kato H
中科院分区：
文献类型：
--
作者：
Miyoshi M;Imakado Y;Otani L;Kaji M;Aanzai Y;Sugimoto N;Murakami T;Fukuoka M;Hohjoh H;Jia H;Kato H
我们先前证明，子宫内蛋白质限制诱导的盐敏感性高血压和改变肾血管紧张素2型受体（AT 2 R）的水平在卒中易感性自发性高血压大鼠（SHRSP）。在这里，我们研究了AT 2 R的这种特征性改变是否与AT 2 R DNA甲基化谱有关。首先，我们在体外研究了AT 2 R DNA甲基化与其启动子活性之间的关系。荧光素酶检测显示这两个变量之间呈负相关。接下来，我们在怀孕期间给SHRSP母鼠和母鼠喂食对照20%酪蛋白饮食或9%酪蛋白饮食。向成年后代和祖代后代提供水或1%生理盐水溶液，持续2周。在喂食低酪蛋白饮食的母亲的成年后代中，TATA-box附近的肾脏AT 2 R启动子DNA甲基化不足，mRNA表达受到抑制，蛋白质表达倾向于更高。此外，盐负荷后，成年祖代表现出高血压，沿着AT 2 R mRNA转录抑制和翻译蛋白升高。在蛋白质限制的胎儿环境下，由于AT 2 R启动子区域的低甲基化而导致的蛋白质表达的增加作为对盐敏感性增加的响应而发生，并且控制这种机制对于预防高血压可能是重要的。在妊娠期间喂食低蛋白饮食的大鼠的后代和子代在饮用盐溶液后显示血压显著升高（增加盐敏感性高血压的风险）。作为一种潜在的分子机制，我们发现调节血压的AT 2 R水平通过启动子区域的DNA低甲基化而增加。控制这种响应盐负荷的特征性变化有助于预防和治疗高血压。
We previously demonstrated that protein restriction in utero induced salt‐sensitive hypertension and changed renal levels of angiotensin type 2 receptor (AT2R) in Stroke‐Prone Spontaneously Hypertensive Rat (SHRSP). Here, we investigated if this characteristic alteration of AT2R is related to AT2R DNA methylation profiles. First, we examined the relation between AT2R DNA methylation and its promoter activity in vitro. Luciferase assays revealed a negative correlation between these two variables. Next, we fed SHRSP dams and grand‐dams a control 20% casein diet or a 9% casein diet during pregnancy. Adult offspring and grand‐offspring were supplied either water or 1% saline solution for 2 weeks. Renal AT2R promoter DNA near the TATA‐box was hypomethylated, mRNA expression was suppressed, and protein expression tended to be higher, in adult offspring of mothers fed a low casein diet. Moreover, adult grand‐offspring exhibited high blood pressure after salt loading, along with suppressed transcription of AT2R mRNA and elevated translated protein. Under a fetal environment of protein restriction, the increase in protein expression due to hypomethylation of the AT2R promoter region occurs as a response to increased salt sensitivity, and controlling this mechanism may be important for the prevention of hypertension. Offspring and grand‐offspring derived from rats fed low‐protein diets during pregnancy showed significantly increased blood pressure upon drinking saline solution (increasing the risk of salt‐sensitive hypertension). As a potential molecular mechanism, we found that the AT2R level that regulates blood pressure is increased through DNA hypomethylation in the promoter region. Controlling this characteristic change observed in response to salt loading could help prevention and treatment of hypertension.
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影响因子：
5.8
作者：
Reinemund, Jana;Seidel, Kerstin;Funke-Kaiser, Heiko
通讯作者：
Funke-Kaiser, Heiko
DOI：
10.1161/hypertensionaha.108.124198
发表时间：
2009-02
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Padia SH;Kemp BA;Howell NL;Gildea JJ;Keller SR;Carey RM
通讯作者：
Carey RM
通过未翻译基因区域和其他非编码元件调节真核基因表达。
影响因子：
8
作者：
Barrett, Lucy W.;Fletcher, Sue;Wilton, Steve D.
通讯作者：
Wilton, Steve D.
DOI：
10.1177/1470320312443720
发表时间：
2012-09
期刊：
Journal of the renin-angiotensin-aldosterone system : JRAAS
影响因子：
--
作者：
Gao J;Chao J;Parbhu KJ;Yu L;Xiao L;Gao F;Gao L
通讯作者：
Gao L
影响因子：
8.3
作者：
Hilliard, Lucinda M.;Chow, Charis L. E.;Denton, Kate M.
通讯作者：
Denton, Kate M.