Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovak Republic.
Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases Inc., Košice, Slovak Republic.
Anticancer Res. 2020 Jun;40(6):3191-3201. doi: 10.21873/anticanres.14300.
BACKGROUND/AIM: Although it has been accepted that the tandem repeat galectin-8 (Gal-8) is linked to angiogenesis, the underlying mechanisms in endothelial cells has remained poorly understood. In this study we aimed to investigate the effect of Gal-8 on selected biological processes linked to angiogenesis in in vitro and in vivo models.
In detail, we assessed how exogenously added human recombinant Gal-8 (with or without vascular endothelial growth factor - VEGF) affects selected steps involved in vessel formation in human umbilical vein endothelial cells (HUVECs) as well as using the chick chorioallantoic membrane (CAM) assay. Gene expression profiling of HUVECs was performed to extend the scope of our investigation.
Our findings demonstrate that Gal-8 in combination with VEGF enhanced cell proliferation and migration, two cellular events linked to angiogenesis. However, Gal-8 alone did not exhibit any significant effects on cell proliferation or on cell migration. The molecular analysis revealed that Gal-8 in the presence of VEGF influenced cytokine-cytokine receptor interactions, HIF-1 and PI3K/AKT signaling pathways. Gal-8 alone also targeted cytokine-cytokine receptor interactions, but with a different expression profile as well as a modulated focal adhesion and TNF signaling.
Gal-8 promotes a pro-angiogenic phenotype possibly in a synergistic manner with VEGF.
背景/目的:尽管串联重复半乳糖凝集素-8(Gal-8)与血管生成有关已被普遍接受,但内皮细胞中潜在的机制仍知之甚少。在本研究中,我们旨在研究 Gal-8 对体外和体内模型中与血管生成相关的选定生物学过程的影响。
详细地,我们评估了外源性添加的人重组 Gal-8(有或没有血管内皮生长因子-VEGF)如何影响人脐静脉内皮细胞(HUVEC)中血管形成所涉及的选定步骤,以及使用鸡胚绒毛尿囊膜(CAM)测定法。我们进行了 HUVEC 的基因表达谱分析,以扩展我们研究的范围。
我们的研究结果表明,Gal-8 与 VEGF 联合增强了细胞增殖和迁移,这两个与血管生成有关的细胞事件。然而,Gal-8 本身对细胞增殖或细胞迁移没有任何显著影响。分子分析表明,Gal-8 在 VEGF 存在的情况下影响细胞因子-细胞因子受体相互作用、HIF-1 和 PI3K/AKT 信号通路。Gal-8 本身也靶向细胞因子-细胞因子受体相互作用,但具有不同的表达谱以及调制的粘着斑和 TNF 信号。
Gal-8 可能以协同方式促进促血管生成表型,与 VEGF 协同作用。