科研星球

细胞信号通路详解:VEGF信号通路

EGF Signaling Pathway

VEGF信号通路‍


Vascular endothelial growth factors (VEGFs) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in the adult. VEGF is produced by several cell types such as fibroblasts, inflammatory cells, and many tumor cells, often in response to increasing tumor hypoxia via the HIF-1a pathway. 

血管内皮生长因子(VEGF)是成人中健康和疾病期间血管发育和血液及淋巴管功能的主要调节因子。VEGF由几种细胞类型如成纤维细胞,炎性细胞和许多肿瘤细胞产生,通常响应于通过HIF-1a途径增加的肿瘤缺氧。



 VEGFHIF-1a和肿瘤的关系


恶性肿瘤的发生与细胞的过度增殖有关,而肿瘤增殖需要大量耗氧,所以肿瘤组织乏氧是恶性肿瘤的重要生物学特征。瘤细胞内对缺氧条件下作出应激反应的许多基因受HIF-1a调控,研究表明HIF-1a与肿瘤的生长繁殖、侵袭和转移、新生血管生成、凋亡、耐药等特征都密切相关。VEGF在肿瘤血管形成中起关键作用,在缺氧时调节VEGF的信号传导途径中,HIF-1a起中枢纽带作用,他的功能不仅使VEGFmRNA稳定性增加,而且能增加VEGF的转录活性。

Currently, the VEGF family is composed of five structurally related factors: VEGFA (most well characterized and denoted VEGFA165), VEGFB, VEGFC, VEGFD and placenta growth factor (PlGF). The VEGF family members are homodimeric polypeptides although naturally occurring heterodimers of VEGFA and PlGF have been described. The main VEGF receptor on endothelial cells is VEGFR2. VEGFR2 is essential for endothelial cell biology during development and in the adult, in physiology and pathology. More is known about VEGFR2 signaling than for the other VEGF receptors. 

目前,VEGF家族由五个结构相关因子组成:VEGFA(也称为VEGFA165,并且研究最为充分),VEGFBVEGFCVEGFD和胎盘生长因子(PlGF)。VEGF家族成员主要以同型二聚体多肽形式存在,尽管天然异二聚体的VEGFAPlGF也已经被报到。内皮细胞上的主要VEGF受体是VEGFR2VEGFR2对于发育期间和成人,生理学和病理学中的内皮细胞生物学研究是重要的靶标。目前关于VEGF受体的研究还是以VEGFR2信号传导较多。


下载.jpeg



In VEGFA165-mediated signal transduction of VEGFR2, the coordinated arrangement of endothelial cells in three dimensions to form and maintain a vascular tube requires endothelial cell proliferation, migration, survival, and permeability. These biological responses are mediated mainly by VEGFA-activated VEGFR2, via a complex network of intracellular signal transduction pathways. On VEGFA-binding to extracellular Ig-like domains 2 and 3 of VEGFR2, signaling molecules bind to phosphorylation sites in the intracellular domain of VEGFR2 and activate downstream mediators resulting in biological responses such as proliferation, migration, survival and permeability.

VEGFA165介导的VEGFR2信号转导中,内皮细胞在三维上的协调排列以形成和维持血管,需要内皮细胞增殖,迁移,存活和渗透。这些生物反应主要由VEGFA激活的VEGFR2通过细胞内信号转导途径的复杂网络介导。在VEGFAVEGFR2的细胞外Ig样结构域23结合时,信号分子与VEGFR2的细胞内结构域中的磷酸化位点结合并激活下游介质,导致生物反应,例如增殖,迁移,存活和渗透。


Activation of the VEGF pathway has been identified in many disease processes ranging from cancer to autoimmunity, retinopathy and many more. The development of highly specific inhibitors of both the VEGF ligand (bevacizumab, VEGF-Trap, ranibizumab) as well as the VEGF receptor (cediranib, pazopanib, sorafenib, sunitinib, vandetanib, axitinib, telatinib, semaxanib, motesanib, vatalanib, Zactima) relates to the central role that this pathway plays in disease.

目前已经在许多疾病过程中鉴定到了VEGF途径的激活,所述疾病过程范围从癌症到自身免疫,视网膜病等。VEGF配体(贝伐单抗,VEGF-Trap,雷珠单抗)以及VEGF受体(西地尼布,帕唑帕尼,索拉非尼,舒尼替尼,凡德他尼,阿西替尼,telatinibsemaxanib,莫特塞尼,瓦塔莱尼,扎卡蒂)的高度特异性抑制剂的开发涉及该途径在疾病中发挥的核心作用。



下载 (1).jpeg

IHC-P staining of mouse lymph node tissue using orb11557 VEGFR2 antibody


下载 (2).jpeg

Immunofluorescence analysis of Hela cells using VEGFA antibody orb333880(green)



没有账号?