Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia.

Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia.
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肾素(原)受体细胞内信号传导与先兆子痫发病机制的关系。

DOI:
10.18926/amo/57374
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发表时间:
2019
影响因子:
0.5
通讯作者:
H. Masuyama
H. Masuyama
中科院分区:
医学4区
文献类型:
--
作者:
Shoko Tamada;T. Mitsui;Akiko Ohira;Kazumasa Tani;Jota Maki;Takeshi Eguchi;Eriko Eto;K. Hayata;H. Masuyama

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最近报道了先兆子痫和(原)肾素之间的关联。(P)RR的细胞内信号传导增加TGF-β和派-1的表达。在这项研究中,我们试图澄清参与(原)肾素在先兆子痫的发病机制,通过细胞内信号(P)RR先兆子痫胎盘。比较了患有先兆子痫的孕妇(n=15)和没有先兆子痫的孕妇(n=28)的活化(原)肾素血浆浓度。用抗HIF-1α和抗(P)RR抗体对胎盘进行免疫组织化学评价。在缺氧条件下培养HTR-8/SVneo细胞,并用人重组(原)肾素处理。实时荧光定量PCR检测HIF-1α、(P)RR、派-1、TGF-β和ET-1 mRNA的表达。在子痫前期患者中,活化的(原)肾素血浆浓度在第三妊娠期显著高于第二妊娠期。HIF-1α和(P)RR在子痫前期胎盘组织中的表达均明显增高。在使用重组(原)肾素的实验中,派-1、TGF-β和ET-1的mRNA表达与缺氧条件相比显著增加。(P)RR在先兆子痫胎盘中的表达通过持续缺氧通过第二和第三孕期增加,并且派-1、TGF-β和ET-1的产生通过(P)RR增加。我们的研究结果表明,ET-1的生产通过细胞内信号(P)RR是重要的发病机制先兆子痫。
An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.
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