FrzA是一种分泌的纹相关蛋白质,诱导了血管新生反应
Pascale Dufourcq1, Thierry Couffinhal, Jérome Ezan
1Inserm U441, Pessac, France. pascale.dufourcq@biophar.u-bordeaux2.fr
Circulation
|December 11, 2002
概括
分泌的纹相关蛋白-1 (FrzA) 促进血管形成 (血管生成). 这表明Wnt信号在血管发育和疾病中起作用.
科学领域:
- 血管生物学 血管生物学
- 信号通道的信号通道.
- 发育生物学是发展生物学.
背景情况:
- 分泌的状相关蛋白 (sFRP) 是Wnt信号的可溶性调制剂.
- sFRP-1/FrzA在血管化过程中表达,并影响血管细胞增殖.
研究的目的:
- 研究sFRP-1/FrzA在血管生成中的作用.
- 探索Wnt信号在血管发育中的参与.
主要方法:
- 在卵巢血管生成过程中分析sFRP-1表达.
- 在体内小胆质膜测定.
- 在体内基因转移研究 (AdFrzA) 在介质细胞和质瘤细胞中.
- 在体外内皮细胞测定 (迁移,管形成,细胞亡).
主要成果:
- sFRP-1表达与卵巢周期期间的新血管化相关.
- 施用FrzA诱导了体内血管生成,增加了血管密度,大小和成熟度.
- 在体外,FrzA增强了内皮细胞迁移,管形成和生存率.
- FrzA的益血管效应独立于常见的生长因子和Akt激活,但涉及减少GSK-3酸化.
结论:
- FrzA表现出显著的益血管效应.
- Wnt信号与正常血管分化和病态血管生成有关.
相关概念视频
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...
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...
Mechanism of Angiogenesis
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...
Regulation of Angiogenesis and Blood Supply
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 hydroxylase and factor...
TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


