内皮激活转录因子3促进了小鼠视网膜中的血管生成和血管修复
Chihiro Ueda1, Susumu Sakimoto1,2, Masahito Yoshihara3,4
1Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
iScience
|January 10, 2025
概括
激活转录因子3 (ATF3) 对于修复视网膜血管至关重要. 降低ATF3的调节会损害血管网络的形成,并阻碍视网膜血管疾病的修复.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 血管生物学 血管生物学
背景情况:
- 视网膜血管疾病导致视力丧失,原因是缺血和病态血管生成.
- 识别血管修复的转录调节剂对于开发新疗法至关重要.
研究的目的:
- 研究激活转录因子3 (ATF3) 在血管生成和血管再生中的作用.
- 阐明ATF3影响视网膜血管修复的机制.
主要方法:
- 在发展期间和血管内皮生长因子刺激后,研究了视网膜血管内皮细胞 (ECs) 中的ATF3表达.
- 评估ATF3下调对体外和体内血管网络形成的影响.
- 利用氧气诱导视网膜病变的小鼠模型来检查ATF3在视网膜血管修复和病理性新血管化中的作用.
- 进行了转录组分析,以确定参与血管生成的ATF3-调节基因.
主要成果:
- 在血管发育过程中,ATF3在视网膜EC中特别表达,并通过血管内皮生长因子进行上调.
- 在体外和体内,ATF3的下调会损害血管网络的形成.
- 在氧诱导视网膜病变模型中,ATF3删除抑制了视网膜血管修复.
- 转录组分析显示,ATF3在EC中高调血管生成相关基因.
结论:
- 在视网膜血管修复中,ATF3起着重要作用.
- 在视网膜血管疾病中,ATF3可以作为促进血管修复的治疗标.
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
5.2K
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...
5.2K