Knocking Out of CEACAM1 Can Reduce Oxidative Stress and Promote Cell Proliferation in the HPMVECs under Hypoxia.
Knocking Out of CEACAM1 Can Reduce Oxidative Stress and Promote Cell Proliferation in the HPMVECs under Hypoxia.
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DOI：
10.1155/2022/1748793
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发表时间：
2022
影响因子：
4.1
通讯作者：
Wang, Jing
中科院分区：
文献类型：
--
作者：
Li, Zhixuan;He, Xiaokang;Zhang, Xueting;Zou, Junhua;Li, Hao;Wang, Jing
缺氧引起的肺动脉高压（PH）在临床实践中很常见，通常提示预后不良。缺氧引起的氧化应激和肺血管内皮细胞增殖是PH病理生理过程中的主要机制，近年来有研究发现癌胚抗原相关细胞粘附分子1（CEACAM 1）促进血管生成。在这项研究中，正常人肺微血管内皮细胞（HPMVEC）和通过CRISPR-Cas9稳定敲除CEACAM 1的HPMVEC经历氧-葡萄糖剥夺/再灌注（OGD/R）以诱导缺氧条件。使用流式细胞术分析每个细胞系和对照的JC-1、ROS和细胞周期谱。采用管形成试验检测血管生成，沿着CEACAM 1、TNF-α、VEGF、VEGFR-2、p-P38/P38和CyclinD 1蛋白的表达水平（以区分血管生成生长和细胞增殖的特征）。我们观察到OGD/R后HPMVEC中CEACAM 1的表达增加，而CEACAM 1 −/− HPMVEC中OGD/R后ROS产生减少，线粒体膜电位增加。此外，我们观察到CEACAM−/− HPMVEC中细胞分裂增加，伴随着血管生成增强和TNF-α蛋白表达减少以及VEGF、VEGFR-2和CyclinD 1表达增加。总之，这些数据表明，缺氧条件下HPMVEC中CEACAM 1的上调可能通过增加氧化应激和抑制细胞增殖来损伤细胞。
Pulmonary hypertension (PH) induced by hypoxia is common in clinical practice and often suggests a poor prognosis. The oxidative stress and proliferation of pulmonary vascular endothelial cells caused by hypoxia are the major mechanisms involved in the pathophysiology of PH. It has been reported in recent years that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes angiogenesis. In this study, normal human pulmonary microvascular endothelial cells (HPMVECs) and HPMVECs with stable knockout of CEACAM1 by CRISPR-Cas9 were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to induce hypoxic conditions. JC-1, ROS, and cell cycle profile were analyzed for each cell line and controls, using flow cytometry. A tube formation assay was used to detect angiogenesis, along with expression levels of CEACAM1, TNF-α, VEGF, VEGFR-2, p-P38/P38, and CyclinD1 proteins (to distinguish profiles of angiogenic growth and cell proliferation). We observed increased expression of CEACAM1 in HPMVECs after OGD/R, while ROS production was reduced and mitochondrial membrane potential was increased after OGD/R in CEACAM1−/− HPMVECs. Furthermore, we observed increased cell division in CEACAM−/− HPMVECs, accompanied by enhanced angiogenesis and reduced TNF-α protein expression and increased VEGF, VEGFR-2, and CyclinD1 expression. Together, these data suggest that upregulation of CEACAM1 in HPMVECs under hypoxic conditions may damage cells by increasing oxidative stress and inhibiting cell proliferation.
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