尿酸通过抑制Wnt信号通路来扰乱斑马鱼的心脏发育
Yahong Li1, Peiying Yang1, Xin Wang1
1Genetic Medicine Center, Nanjing Women and Children's Healthcare Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Cardiovascular toxicology
|August 21, 2025
概括
高尿酸 (UA) 通过抑制Wnt信号来破坏斑马鱼的先天心脏发育. 增加UA的干预导致心脏缺陷,通过Wnt通路激活部分挽救.
科学领域:
- 发育生物学
- 心血管研究
- 代谢学
背景情况:
- 遗传性心脏病 (CHD) 是一种常见的出生缺陷,
- 尿酸 (尿素代谢物) 在心脏发育中的作用基本上未知.
- 了解影响心脏发育的因素对于预防心脏病至关重要.
研究的目的:
- 在斑马鱼模型中研究高尿酸水平对心脏发育的影响.
- 探索Wnt信号通路在UA诱导的心脏异常中的参与.
- 确定调节Wnt信号是否可以缓解UA相关的心脏缺陷.
主要方法:
- 用于研究心脏发育的斑马鱼模型.
- 通过外源性暴露,xdh过度表达和uox敲击引起的尿酸升高.
- 基因表达分析 Wnt 途径组件,心脏原始标记物和关键发育基因.
- 在受精后72小时内对心脏功能 (心脏周周胀,心率) 的表型评估.
- 使用Wnt激活剂 (CHIR99021) 的药理干预.
主要成果:
- 所有方法都显著增加了斑马鱼的UA度.
- 升高的UA导致心脏表型,包括心周胀和心率下降.
- 超载UA导致Wnt信号和重要心脏发育基因的下调.
- Wnt通路的激活部分挽救了由UA升高引起的心脏缺陷.
结论:
- 尿酸的增加,无论是外源的还是内源的,都会对斑马鱼的心脏发育产生不利影响.
- 抑制Wnt信号是UA破坏心脏形态的关键机制.
- 这些发现突显了代谢与先天性心脏缺陷之间的潜在联系.
相关概念视频
Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...


