叶酸调节平面细胞极性通路和F-actin通过叶酸受体alpha进行调节
Xiao Han1,2, Xuanye Cao2, Robert M Cabrera2
1Department of Reproductive Medicine Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
概括
叶酸 (FA) 促进细胞增殖和F-actin的形成比5-甲基四基酸盐 (5mTHF) 更多. 叶酸受体1 (FOLR1) 增强了Vangl2的转录,揭示了将叶酸缺乏与神经管缺陷联系在一起的机制.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 营养科学 营养科学
背景情况:
- 叶酸缺乏与神经管缺陷 (NTD) 有关,但机制尚不清楚.
- 关于补充叶酸的最佳形式存在争议.
- 叶酸代谢和信号通路对于胚胎发育至关重要.
研究的目的:
- 为了比较叶酸 (FA) 和5-甲基四基叶酸 (5mTHF) 对细胞增殖和F-actin形成的影响.
- 研究叶酸受体1 (FOLR1) 在叶酸介导的细胞过程中的作用.
- 阐明将叶酸状况与神经管缺陷病因学联系起来的分子机制.
主要方法:
- 小鼠胚胎纤维细胞 (MEF) 被培养成不同度的FA和5mTHF.
- 细胞增殖和F-actin形成在三个通道上进行了监测.
- 进行了RNA测序和蛋白质水平分析,以评估信号通路和基因表达.
主要成果:
- 在促进MEF增殖和F-actin形成方面,FA表现出比5mTHF更强的效果.
- FOLR1蛋白水平与叶酸度正相关.
- 叶酸补充丰富了非正规的Wnt/平面细胞极性 (PCP) 信号通路,其中FOLR1促进了Vangl2转录.
结论:
- 与5mTHF相比,FA在支持细胞增殖和F-actin组织方面具有明显的优势.
- 以FOLR1为媒介的Vangl2转录是叶酸在发育中的关键机制.
- 这项研究提供了关于叶酸缺乏如何导致NTD的新见解.
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