Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.
Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.
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DOI：
10.3390/ijms19051413
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发表时间：
2018-05-09
影响因子：
5.6
通讯作者：
Radu BM
中科院分区：
文献类型：
--
作者：
Banciu A;Banciu DD;Mustaciosu CC;Radu M;Cretoiu D;Xiao J;Cretoiu SM;Suciu N;Radu BM
电压门控钙通道和雌激素受体在子宫生理中起着至关重要的作用，它们与不同钙信号通路的关联影响着子宫肌层的健康和病理状况。在人类子宫肌层中存在的各种细胞亚型的特性中，越来越多的证据表明，远端细胞（tc）的钙振荡有助于收缩活动和妊娠。我们的研究旨在评估β -雌二醇对人子宫肌层TCs中电压门控钙通道和雌激素受体的影响，并了解它们在妊娠中的作用。为此，我们采用膜片钳记录、基于比例fura -2的钙成像分析和qRT-PCR技术来分析培养的来自妊娠和非妊娠子宫样本的人子宫内膜tc。在未怀孕和怀孕子宫的人子宫内膜tc中，我们通过qRT-PCR证实了编码电压门控钙通道（Cav3.1, Ca3.2, Cav3.3, Cav2.1），雌激素受体（ESR1, ESR2, GPR30）和核受体共激活因子3 （NCOA3）的基因的存在。与未妊娠相比，妊娠显著上调Cav3.1，下调Cav3.2、Cav3.3、ESR1、ESR2和NCOA3。β -雌二醇处理（24 h、10、100、1000 nM）可下调人妊娠子宫肌层TCs中Cav3.2、Cav3.3、Cav1.2、ESR1、ESR2、GRP30和NCOA3的表达。我们还通过膜片钳记录和灌注BAY K8644的孕妇肌层TCs的钙成像分析证实了电压门控钙通道的功能表达，从而诱导钙通过这些通道流入。此外，我们证明了β -雌二醇（1000 nM）在相同的制剂中拮抗BAY K8644（2.5或5µM）的作用。总之，我们证实了未怀孕和怀孕的人子宫肌层TCs中存在电压门控钙通道和雌激素受体，以及β -雌二醇在怀孕条件下对其基因表达的调节。进一步探索TCs中钙信号及其受雌激素调节的机制，将有助于理解分娩和妊娠机制，并有助于制定有效的策略来降低早产风险。
Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth.
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影响因子：
9.8
作者：
Bernstein, Kyra;Vink, Joy Y.;Fu, Xiao Wen;Wakita, Hiromi;Danielsson, Jennifer;Wapner, Ronald;Gallos, George
通讯作者：
Gallos, George
影响因子：
3.7
作者：
Herington JL;Swale DR;Brown N;Shelton EL;Choi H;Williams CH;Hong CC;Paria BC;Denton JS;Reese J
通讯作者：
Reese J
影响因子：
2.3
作者：
Cretoiu, Sanda Maria;Radu, Beatrice Mihaela;Banciu, Adela;Banciu, Daniel Dumitru;Cretoiu, Dragos;Ceafalan, Laura Cristina;Popescu, Laurentiu Mircea
通讯作者：
Popescu, Laurentiu Mircea
影响因子：
2
作者：
Lee, Si-Eun;Ahn, Duck-Sun;Lee, Young-Ho
通讯作者：
Lee, Young-Ho
DOI：
10.1530/rep-12-0369
发表时间：
2013-04
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Cretoiu SM;Cretoiu D;Marin A;Radu BM;Popescu LM
通讯作者：
Popescu LM