Department of Computational Biology and Bioinformatics, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India.
Cell Biochem Biophys. 2022 Sep;80(3):519-536. doi: 10.1007/s12013-022-01078-0. Epub 2022 Jun 14.
Metabolic status of the cells is important in the expression of the angiogenic phenotype in endothelial cells. Our earlier studies demonstrated the effects of metabolites such as lactate, citrate and lipoxygenase products, on VEGFA-VEGFR2 signaling pathway. Though this link between metabolite status and molecular mechanisms of angiogenesis is becoming evident, it is not clear how it affects genome-level expression in endothelial cells, critical to angiogenesis. In the present study, computational analysis was carried out on the transcriptome data of 4 different datasets where HUVECs were exposed to low and high glucose, both in vitro and in vivo, and the expression of a key enzyme involved in glucose metabolism is altered. The differentially expressed genes belonging to both VEGFA-VEGFR2 signaling pathway, as well as several VEGF signature genes as hub genes were also identified. These findings suggest the metabolite dependence, particularly glucose dependence, of angiogenesis, involving modulation of genome-level expression of angiogenesis- functional genome. This is important in tumor angiogenesis where reprogramming of metabolism is critical.
细胞的代谢状态对于内皮细胞中血管生成表型的表达很重要。我们之前的研究表明，代谢物如乳酸盐、柠檬酸盐和脂氧合酶产物对 VEGFA-VEGFR2 信号通路有影响。尽管代谢物状态与血管生成的分子机制之间的联系变得越来越明显，但目前尚不清楚它如何影响内皮细胞中的基因组水平表达，而这对血管生成至关重要。在本研究中，我们对 4 个不同数据集的转录组数据进行了计算分析，这些数据集分别研究了体外和体内低葡萄糖和高葡萄糖对 HUVEC 的影响，以及改变了参与葡萄糖代谢的关键酶的表达。还鉴定了属于 VEGFA-VEGFR2 信号通路以及几个 VEGF 特征基因的差异表达基因作为枢纽基因。这些发现表明血管生成的代谢物依赖性，特别是葡萄糖依赖性，涉及血管生成功能基因组的基因组水平表达的调节。这在肿瘤血管生成中很重要，因为代谢重编程是关键的。
