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端锚聚合酶抑制作用可调节促性腺激素处理大鼠的黄体发育及黄体功能。

Tankyrase inhibition regulates corpus luteum development and luteal function in gonadotropin-treated rats.

作者信息

Accialini Paula, Irusta Griselda, Bechis Andrés, Bas Diana, Parborell Fernanda, Abramovich Dalhia, Tesone Marta

机构信息

Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.

Departamento de Quıímica Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.

出版信息

Mol Reprod Dev. 2017 Aug;84(8):719-730. doi: 10.1002/mrd.22853. Epub 2017 Jul 13.

DOI:10.1002/mrd.22853
PMID:28628258
Abstract

Tankyrases are physiological regulators of Axin, a protein involved in several cellular processes, including Wnt signaling. Here, we investigated the effect of a specific Tankyrase inhibitor (XAV939) in follicular-luteal dynamics, and its possible relationship with ovarian vascular development. Studies were designed to analyze the effect of intrabursa administration of XAV939 in gonadotropin-treated prepubertal rats. In particular, we examined follicle and corpus luteum development, steroidogenesis, angiogenic markers, and apoptotic parameters. We found that in vivo inhibition of Wnt signaling impaired corpus luteum development, with a decrease in the number of corpora lutea balanced by a high number of cysts; decreased circulating progesterone levels, likely due to a decrease in Steroidogenic acute regulatory protein content in the corpus luteum; and increased pro-apoptotic parameters. In addition, Extracellular signal-regulated kinase phosphorylation, Vascular endothelium growth factor 120 content, and endothelial cell area were diminished in corpora lutea of inhibitor-treated ovaries. Thus, Wnt/β-catenin signaling appears to participate in the regulation of corpus luteum development and luteal cell function.

摘要

端锚聚合酶是轴蛋白的生理调节因子,轴蛋白是一种参与包括Wnt信号传导在内的多种细胞过程的蛋白质。在此,我们研究了一种特异性端锚聚合酶抑制剂(XAV939)对卵泡-黄体动态变化的影响及其与卵巢血管发育的可能关系。研究旨在分析向性腺激素处理的青春期前大鼠的囊内注射XAV939的效果。具体而言,我们检测了卵泡和黄体发育、类固醇生成、血管生成标志物以及凋亡参数。我们发现,体内对Wnt信号传导的抑制损害了黄体发育,黄体数量减少,同时伴有大量囊肿;循环孕酮水平降低,这可能是由于黄体中类固醇生成急性调节蛋白含量减少所致;促凋亡参数增加。此外,在抑制剂处理的卵巢的黄体中,细胞外信号调节激酶磷酸化、血管内皮生长因子120含量以及内皮细胞面积均减少。因此,Wnt/β-连环蛋白信号传导似乎参与了黄体发育和黄体细胞功能的调节。

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Mol Reprod Dev. 2017 Aug;84(8):719-730. doi: 10.1002/mrd.22853. Epub 2017 Jul 13.
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Tankyrase inhibitors attenuate WNT/β-catenin signaling and inhibit growth of hepatocellular carcinoma cells.端锚聚合酶抑制剂减弱WNT/β-连环蛋白信号传导并抑制肝癌细胞生长。
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