通过抑制FGF2/FGFR1通路,VEGF-B可以防止过度血管生成
Chunsik Lee1, Rongyuan Chen1, Guangli Sun2
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, P. R. China.
Signal transduction and targeted therapy
|August 17, 2023
概括
令人惊的是,血管内皮生长因子-B (VEGF-B) 通过阻断FGF2/FGFR1通路来抑制血管生成. 这一发现影响了对神经血管疾病的理解和治疗.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 血管内皮生长因子-B (VEGF-B) 是VEGF-A的同源,尽管它在新血管疾病中受到抑制,但其血管新生效应尚不清楚.
- 目前针对VEGF家族成员的治疗策略需要更清楚地了解VEGF-B的具体作用.
研究的目的:
- 阐明VEGF-B的精确血管生成功能和分子机制.
- 研究VEGF-B与FGF2/FGFR1信号通路的相互作用.
主要方法:
- 使用了全面的体外和体外实验模型.
- 分析了分子相互作用,包括蛋白质结合和信号通路激活 (例如,Erk激活).
主要成果:
- 已证明,在高FGF2/FGFR1表达的条件下,VEGF-B作为血管生成的内源性抑制剂.
- 揭示了VEGF-B与纤维细胞生长因子受体1 (FGFR1) 结合,诱导FGFR1/VEGFR1复合体的形成.
- 显示VEGF-B抑制了FGF2诱导的Erk激活,从而抑制了FGF2驱动的血管生成和瘤生长.
结论:
- 通过调节FGF2/FGFR1通路,VEGF-B具有对血管生成的新型抑制功能.
- 涉及VEGF-B调制的治疗策略需要仔细考虑,因为它具有取决于环境的抗血管性质.
相关概念视频
Regulation 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
Mechanism of Angiogenesis
5.6K
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...
5.6K
TGF - β Signaling Pathway
7.4K
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...
7.4K
Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K


