取决于切口的VEGFR3上调,可以在没有VEGF-VEGFR2信号的情况下产生血管新生
Rui Benedito1, Susana F Rocha, Marina Woeste
1Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, D-48149 Münster, Germany. rui.benedito@mpi-muenster.mpg.de
Nature
|March 20, 2012
概括
划痕信号差异调节血管内皮生长因子受体 (VEGFRs). 隙抑制对VEGFR3的影响比VEGFR2更大,影响了对血管生成至关重要的内皮芽生殖和增殖.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 血管新生研究的研究.
背景情况:
- 血管内皮生长因子 (VEGFs) 和它们的受体 (VEGFRs) 驱动血管生成.
- VEGF和Notch通路相互连接,VEGF-A诱导DLL4,一个Notch连接体,以调节内皮细胞的行为.
- DLL4-Notch信号通常会抑制VEGFR的表达,以控制发芽和繁殖.
研究的目的:
- 调查Notch信号与VEGFR2/VEGFR3在调节血管生成中的确切关系.
- 为了确定Notch抑制对VEGFR表达和内皮细胞发芽的影响.
- 为了阐明VEGFRs通过Notch信号的差异调节.
主要方法:
- 在活体中诱导性功能丧失遗传学.
- 抑制VEGFR2和诺奇信号通路.
- 对视网膜尖端细胞中DLL4蛋白表达的分析.
- 评估内皮细胞的发芽和增殖.
主要成果:
- 尖端细胞中的DLL4蛋白表达显示了VEGFR2信号的弱调制.
- 缺口抑制没有显著影响VEGFR2表达,但诱导了不受调节的内皮芽生殖和增殖.
- VEGFR3被Notch强烈调节;在低Notch条件下,VEGFR3抑制剂抑制了发芽.
- 通过Notch信号,VEGFR2和VEGFR3受到不同的调节.
结论:
- 缺口信号显示了VEGFR2和VEGFR3.3的不同调节.
- VEGFR2对于内皮芽发育和增殖的Notch介导调节是不可或缺的.
- 针对血管新生需要考虑内皮内的Notch信号状态.
相关概念视频
Regulation of Angiogenesis and Blood Supply
3.0K
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...
3.0K
Mechanism of Angiogenesis
6.2K
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...
6.2K
Notch Signaling Pathway
4.7K
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...
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...
4.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.2K
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...
2.2K
TGF - β Signaling Pathway
8.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.2K
Non-Canonical Wnt Signaling Pathways
7.8K
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...
7.8K


