Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction.
Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction.
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DOI：
10.3390/medicina56120722
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发表时间：
2020-12-21
期刊：
影响因子：
--
通讯作者：
Ikeda T
中科院分区：
文献类型：
--
作者：
Tsuchiya K;Tanaka K;Tanaka H;Maki S;Enomoto N;Takakura S;Nii M;Toriyabe K;Katsuragi S;Ikeda T
背景和目标：胎儿生长受限（FGR）与胎儿死亡率相关，是脑瘫和未来生活方式相关疾病的危险因素。尽管进行了广泛的研究，但FGR没有有效的治疗策略。哺乳动物雷帕霉素靶蛋白（mTOR）信号传导对胎儿器官的生长非常重要，其失调与流产有关。在这里，我们专注于mTOR信号传导，并研究了磷酸核糖体蛋白S6（rps 6）和磷酸真核翻译起始因子4 E（eIF-4 E）的活性，它们在人胎盘中作用于mTOR信号传导的下游，在他达拉非治疗FGR后如何变化，旨在阐明潜在的作用机制。通过缺氧诱导因子（HIF）-2α的免疫组化染色研究胎盘缺氧。材料与方法：分别用Western blotting和酶联免疫吸附试验检测磷酸化rps 6和磷酸化eIF 4 E的表达。结果如下：FGR胎盘组织中HIF-2α的表达显著高于对照组，但在他达拉非治疗后降至对照组水平。FGR胎盘中磷酸化rps 6和磷酸化eIF-4 E的水平显著高于对照胎盘，但在他达拉非治疗后降至对照水平。结论：他达拉非使FGR胎盘中HIF-2α、磷酸化rps 6和eIF-4 E的水平恢复至对照胎盘中观察到的水平，表明其可能是FGR的一种有前景的治疗策略。
Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
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DOI：
10.1016/j.bpobgyn.2018.02.009
发表时间：
2018-05-01
影响因子：
5.5
作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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DOI：
10.1083/jcb.201306041
发表时间：
2013-11-25
期刊：
The Journal of cell biology
影响因子：
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通讯作者：
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