通过CXCR3-CXCL11信号,限制了血管生成,并促进了细胞周围细胞的招募
Megan E Goeckel1,2, Jihui Lee1, Allison Levitas1
1Department of Cell Biology and Physiology, Washington University School of Medicine St. Louis, MO, 63110.
bioRxiv : the preprint server for biology
|September 25, 2023
概括
血流通过CXCR3和CXCL11调节内皮细胞 (EC) 信号,影响细胞周围细胞的招募和血管的发育. 这项研究揭示了CXCR3的存在.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 发育生物学是发展生物学.
背景情况:
- 内皮细胞 (EC) - 细胞相互作用对于血管重塑至关重要.
- 血动力学力量影响EC-pericyte相互作用,但基本的信号通路尚不清楚.
- 了解这些途径是解决血管发育和疾病的关键.
研究的目的:
- 通过血流调节的EC中识别新型信号网络.
- 研究化学因子受体CXCR3及其配体CXCL11在EC-pericyte相互作用中的作用.
- 阐明CXCR3信号影响血管生成潜力和细胞周围细胞招募的机制.
主要方法:
- 在体外建模EC-pericyte共同培养.
- 使用Cxcr3抑制的斑马鱼模型进行体内研究 (AMG487).
- 流量建模平台,以评估EC行为和细胞-细胞结合点.
主要成果:
- 在EC中发现了一种涉及CXCR3和CXCL11的新型信号网络,该网络调节pdgfb的表达.
- 抑制EC特异性CXCR3信号传递导致体内减少了与EC管的细胞周关联.
- 在体内,斑马鱼的Cxcr3抑制导致皮质细胞协会受损和血管扩张,特别是在头骨血管系统中.
- 缺乏CXCR3的EC在流动条件下表现出改变的形态,较慢的迁移和受损的细胞-细胞结合.
结论:
- 在EC中CXCR3信号传递在抑制血管新生潜力和细胞周围细胞招募方面发挥着关键作用.
- 这种信号通路在发育过程中对血管稳定至关重要.
- 准CXCR3可能为血管相关疾病提供治疗策略.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K
01:10Mechanism of Angiogenesis
5.5K
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...
5.5K
01:24Overview of Cell-Matrix Interactions
7.3K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.3K
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
02:33Hedgehog Signaling Pathway
7.4K
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...
7.4K