Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.
Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.
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DOI：
10.1016/j.cell.2013.12.025
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发表时间：
2014-01-30
期刊：
影响因子：
64.5
通讯作者：
Iruela-Arispe ML
中科院分区：
文献类型：
--
作者：
Goddard LM;Murphy TJ;Org T;Enciso JM;Hashimoto-Partyka MK;Warren CM;Domigan CK;McDonald AI;He H;Sanchez LA;Allen NC;Orsenigo F;Chao LC;Dejana E;Tontonoz P;Mikkola HK;Iruela-Arispe ML
血管通透性通常与炎症相关，并由一组分泌的通透性因子（如VEGF）触发。在这里，我们表明，植入前的生理血管通透性是直接控制孕激素受体（PR），是独立的VEGF。PR的全局和内皮特异性缺失都阻断了子宫中的生理血管通透性，而PR在其他器官的内皮中的错误表达导致异位血管渗漏。整合内皮全基因组转录谱与ChIP测序显示，PR诱导NR 4A 1（Nur 77/TR 3）依赖性转录程序，广泛调节血管通透性，响应孕酮。NR 4A 1的沉默阻断PR介导的渗透性反应，表明PR和NR 4A 1之间的直接联系。该程序触发几种连接蛋白的同时抑制，并导致对胚胎植入至关重要的血管屏障功能的有效、及时和静脉特异性调节。
Vascular permeability is frequently associated with inflammation and triggered by a cohort of secreted permeability factors such as VEGF. Here we show that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus whereas misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of an endothelial genome-wide transcriptional profile with ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3)-dependent transcriptional program that broadly regulates vascular permeability in response to progesterone. Silencing of NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venous-specific regulation of vascular barrier function that is critical to embryo implantation.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
DOI：
10.1016/0960-0760(95)00091-d
发表时间：
1995-06-01
影响因子：
4.1
作者：
EDWARDS, DP;ALTMANN, M;BECK, CA
通讯作者：
BECK, CA
影响因子：
4.8
作者：
Franco, Heather L.;Rubel, Cory A.;DeMayo, Francesco J.
通讯作者：
DeMayo, Francesco J.
影响因子：
6.1
作者：
Kovacs, G
通讯作者：
Kovacs, G
影响因子：
4.8
作者：
Behrmann, I;Smyczek, T;Haan, C
通讯作者：
Haan, C