瓦尔酸提高了HIF-1α介导的CGB表达,并抑制了BeWo细胞的葡萄糖吸收
Go Kitahara1, Kazuma Higashisaka1,2, Yurina Nakamoto1
1Graduate School of Pharmaceutical Sciences, Osaka University.
The Journal of toxicological sciences
|January 31, 2024
概括
酸 (VPA) 通过改变激素的产生和葡萄糖的吸收来破坏胎盘功能. 这种化学毒性会影响关键的胎盘通路,可能会影响怀孕健康.
科学领域:
- 生殖生物学 生殖生物学
- 毒理学 毒理学 毒理学
- 细胞和分子生理学的细胞和分子生理学.
背景情况:
- 胎盘功能障碍可能会对怀孕结果产生负面影响.
- 有限的研究存在于影响胎盘功能的化学诱导毒性.
- 瓦尔酸 (VPA) 是一种已知的原体,因此它是一个相关的示范化学物质.
研究的目的:
- 研究酸 (VPA) 对人类胎盘细胞中激素产生和葡萄糖吸收的影响.
- 阐明潜在的分子机制,特别是HIF-1α的作用.
- 评估HIF-1α调制的潜力,以逆转VPA诱导的胎盘变化.
主要方法:
- 人类胆瘤 BeWo 细胞通过使用福斯科林分化为合成细胞.
- 随后,细胞用酸 (VPA) 治疗72小时.
- 实时RT-PCR,RNA-seq和通路分析被用于评估基因表达和蛋白质水平. 化被用来调节HIF-1α.
主要成果:
- VPA显著增加了胆性淋巴激素β (CGB) 的mRNA表达.
- VPA抑制了福斯科林诱导的细胞内葡萄糖吸收和GLUT1水平的增加.
- VPA降低了HIF-1α蛋白水平及其下游目标 (HK2,ADM),这表明它在缺氧途径中发挥了作用. 化可以逆转这些效应.
结论:
- 酸 (VPA) 通过一种涉及HIF-1α的新机制诱导胎盘功能障碍.
- VPA提高了CGB的表达,并通过HIF-1α介导的途径抑制了葡萄糖的摄取.
- 了解这些机制对于评估怀孕期间的化学风险至关重要.
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