Activation of ERK pathway is required for 15-HETE-induced angiogenesis in human umbilical vascular endothelial cells.
Activation of ERK pathway is required for 15-HETE-induced angiogenesis in human umbilical vascular endothelial cells.
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15-HETE 诱导人脐血管内皮细胞血管生成需要激活 ERK 通路
DOI：
10.3109/10799893.2015.1077865
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhu Daling
中科院分区：
文献类型：
--
作者：
Wang Shuang;Cao Weiwei;Xing Hao;Chen Ying Li;Li Qian;Shen Tingting;Jiang Chun;Zhu Daling
血管生成在心血管疾病、视网膜缺血或肿瘤发生的进展中起着关键作用。内皮细胞增殖和凋亡的不平衡扰乱了血管生成的建立，而血管生成受到多种花生四烯酸代谢物的影响。 15-羟基二十碳四烯酸（15-HETE）是其中一种代谢物。然而，15-HETE 在人脐血管内皮细胞 (HUVEC) 中诱导血管生成的潜在机制仍知之甚少。由于细胞外信号调节激酶 (ERK) 是细胞增殖的关键调节因子，因此 HUVEC 中 15-HETE 调节血管生成过程和 ERK 增殖效应之间可能存在串扰。为了检验这一假设，我们使用细胞活力测量、细胞周期分析、蛋白质印迹、划伤、管形成测定和核形态测定来研究 15-HETE 对细胞增殖、血管生成和细胞凋亡的影响。我们发现 15-HETE 促进 HUVEC 血管生成，这是由 ERK 介导的。此外，15-HETE诱导增殖和细胞周期从G0/G1期向G2/M + S期的转变。使用 PD98059（一种 ERK 抑制剂）阻断 ERK 后，所有这些影响都被逆转。此外，15-HETE 通过 ERK 途径缓解 HUVEC 凋亡。因此，ERK对于15-HETE调节HUVEC血管生成的作用是必要的，这可能是治疗血管生成相关疾病的新的潜在靶点。
Angiogenesis plays a critical role in the progression of cardiovascular disease, retinal ischemia, or tumorigenesis. The imbalance of endothelial cell proliferation and apoptosis disturbs the establishment of the vasculogenesis, which is affected by several arachidonic acid metabolites. 15-Hydroxyeicosatetraenoic acid (15-HETE) is one of the metabolites. However, the underlying mechanisms of angiogenesis induced by 15-HETE in human umbilical vascular endothelial cells (HUVECs) are still poorly understood. Since extracellular signal-regulated kinase (ERK) is a critical regulator of cell proliferation, there may be a crosstalk between 15-HETE-regulating angiogenic process and ERK-proliferative effect in HUVECs. To test this hypothesis, we study the effect of 15-HETE on cell proliferation, angiogenesis, and apoptosis using cell viability measurement, cell cycle analysis, western blot, scratch–wound, tube formation assay, and nuclear morphology determination. We found that 15-HETE promoted HUVEC angiogenesis, which were mediated by ERK. Moreover, 15-HETE-induced proliferation and cell cycle transition from the G0/G1phase to the G2/M + S phase. All these effects were reversed after blocking ERK with PD98059 (an ERK inhibitor). In addition, HUVEC apoptosis was relieved by 15-HETE through the ERK pathway. Thus, ERK is necessary for the effects of 15-HETE in the regulation of HUVEC angiogenesis, which may be a novel potential target for the treatment of angiogenesis-related diseases.