相关实验视频
Updated: Jun 16, 2025
06:51
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
5.3K
在PIK3CA驱动的耐火性血管形中,胚胎细胞起源和缺氧介导的机制
Sota Torii1, Keiki Nagaharu2, Nanako Nakanishi1
1Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
EMBO molecular medicine
|April 15, 2025
概括
头部和部的先天性血管形是由心膜中皮产生的. 在这个胚胎组织中激活Pik3ca会通过缺氧和VEGF-A信号传递驱动血管异常生长.
科学领域:
- 发育生物学是发展生物学.
- 血管生物学 血管生物学
- 分子遗传学 分子遗传学
背景情况:
- 先天性血管形影响0.5%的人口,经常发生在头部和部.
- 由于头部和部结构的关键功能,这些形带来了治疗挑战.
- 之前的研究确定了心膜间皮 (CPM) 作为头部和部血液和淋巴血管的来源.
研究的目的:
- 调查源自CPM的先天性血管形的发病原因.
- 确定Pik3ca信号在CPM衍生的血管发育中的作用.
- 为了探索头部和部血管形的治疗点.
主要方法:
- 在CPM中使用了一个表达Pik3caH1047R的鼠标模型.
- 采用单细胞RNA测序来分析内皮细胞中的基因表达变化.
- 检查了人类形样本,用于分子途径验证.
- 测试了针对HIF-1α和VEGF-A通路的治疗干预措施.
主要成果:
- 在CPM中的Pik3caH1047R表达导致小鼠的头部和部特定的血管异常.
- 通过HIF介导的缺氧信号,对VEGF-A的升调被确定为一个关键机制.
- 在人类血管形中证实了HIF-1α和VEGF-A水平的升高.
- 在小鼠模型中,抑制HIF-1α和VEGF-A显著改善了异常血管系统.
结论:
- 来自CPM的胚胎起源对于头部和部血管形至关重要.
- 缺氧驱动的信号通路,特别是涉及HIF-1α和VEGF-A,是关键的驱动因素.
- 针对HIF-1α和VEGF-A为这些疾病提供了一个有前途的治疗策略.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:10Mechanism of Angiogenesis
5.4K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.4K
01:07Development of Blood Vessels
553
The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
553