高血糖症通过降低细胞内pH值诱导左右轴的饮食依赖缺陷
Ryohei Matsuoka1, Keiko Kitajima2, Takenobu Nii2
1Department of Developmental Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Biochimica et biophysica acta. Molecular basis of disease
|October 23, 2024
概括
孕产妇糖尿病可以通过扰乱胚胎的左右身体轴引起先天性异常,如异质毒性综合征. 高血糖水平会损害Wnt信号和节点表达,导致器官排列缺陷.
科学领域:
- 发展生物学 发展生物学
- 胚胎学 胚胎学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 孕期糖尿病是已知的先天性异常的风险因素.
- 异质性综合征是一种罕见的先天性缺陷,涉及沿着身体左右轴的异常器官安排,与孕产妇糖尿病有关.
- 连接母婴糖尿病与异质毒素的确切机制仍然不完全理解.
研究的目的:
- 研究母婴糖尿病在小鼠胚胎中诱导异质毒性综合征的分子机制.
- 阐明左右 (L-R) 轴形成途径在糖尿病诱导胚胎病变中的作用.
主要方法:
- 对糖尿病母鼠胚胎中L-R轴形成的分析.
- 对基因表达模式的评估,包括Pitx2和Nodal.
- RNA测序用于识别代谢失调.
- 研究Wnt信号通路活动和原始条纹中的细胞内pH值.
- 评估母亲摄入维生素A的影响.
主要成果:
- 来自糖尿病母的胚胎表现出中断的L-R轴形成与异常的Pitx2表达.
- 节点上的节点表达显著减少,反映了Wnt3a-/-胚胎中的缺陷.
- 规范的Wnt信号被下调,RNA测序揭示了失调的糖解.
- 高血糖水平降低了原始链中的细胞内pH值,抑制了Wnt信号和节点表达.
- 母亲的维生素A摄入量加剧了L-R轴缺陷,表明视网膜酸代谢失调.
结论:
- 孕产妇糖尿病通过受损的Wnt信号和节点表达来破坏胚胎L-R轴的形成,这是由高葡萄糖诱导的代谢变化所驱动的.
- 这些发现阐明了糖尿病相关胚胎病变的潜在机制,特别是异质毒性.
- 饮食因素,如维生素A,可能在预防这些发育缺陷方面发挥关键作用.
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