BMPR2 expression is suppressed by signaling through the estrogen receptor.
BMPR2 expression is suppressed by signaling through the estrogen receptor.
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DOI：
10.1186/2042-6410-3-6
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发表时间：
2012-02-20
影响因子：
7.9
通讯作者：
Lane KB
中科院分区：
文献类型：
--
作者：
Austin ED;Hamid R;Hemnes AR;Loyd JE;Blackwell T;Yu C;Phillips Iii JA;Gaddipati R;Gladson S;Gu E;West J;Lane KB
在多器官系统的研究表明，通过骨形态发生蛋白受体2型（BMPR2）和雌激素途径的信号之间存在交叉对话。在人类中，肺动脉高压（PAH）具有女性优势，并与BMPR2表达降低有关。本研究的目的是确定雌激素是否抑制BMPR2的表达。在多个模型平台上使用了各种技术来评估雌激素与BMPR2基因表达之间的关系。我们在人类样本、活小鼠和细胞培养中使用了定量RT-PCR、凝胶迁移率转移和荧光素酶活性测定。BMPR2在女性患者淋巴细胞中的表达低于男性患者，在雌性小鼠全肺中的表达低于雄性小鼠。在BMPR2启动子中存在一个进化上保守的雌激素受体结合位点，通过凝胶转移实验可以与雌激素受体结合。增加外源性雌激素降低BMPR2在细胞培养中的表达，特别是在诱导增殖时。雌激素受体α转染量增加与BMPR2表达降低密切相关。在活的人和小鼠中，与男性相比，BMPR2基因在女性中的表达减少，可能是通过雌激素受体α与BMPR2启动子的直接结合。BMPR2表达的减少可能导致女性PAH患病率的增加。
Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression. A variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture. BMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2. BMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.