The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.

The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.
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DOI:
10.3390/ph16040500
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发表时间:
2023-03-28
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Gong F
Gong F
中科院分区:
其他
文献类型:
--
作者:
Tao Y;Wang W;Jin Y;Wang M;Xu J;Wang Y;Gong F

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EphrinB 2/EphB 4信号通路涉及血管形态发生和血管生成的调节。然而,EphrinB 2/EphB 4在川崎和冠状动脉瘤形成的发病机制中知之甚少。因此,本研究旨在探讨EphrinB 2/EphB 4在KD冠状动脉内皮损伤中的作用以及EphrinB 2-Fc的潜在治疗作用。比较川崎病患儿和健康儿童EphB 4的表达水平。用急性KD患者血清刺激人冠状动脉内皮细胞(HCAECs),建立KD细胞模型。发现EphB 4的过表达或用EphrinB 2-Fc处理干预细胞模型。检测细胞迁移、血管生成和增殖能力,并检测炎症相关因子的表达。我们的研究表明EphB 4在KD患者和KD细胞模型中均显示低表达。CAA+ KD患儿CEC中EphB 4蛋白水平明显低于健康儿童。EphrinB 2-Fc处理KD血清激活的HCAEC抑制细胞增殖,降低炎症相关因子(如IL-6和P-选择素)的表达,并提高细胞血管生成能力。结果表明EphrinB 2-Fc对血管内皮细胞具有保护作用,在保护KD患者血管内皮方面具有良好的临床应用前景。
The EphrinB2/EphB4 signaling pathway involves the regulation of vascular morphogenesis and angiogenesis. However, little is known about EphrinB2/EphB4 in the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysm formation. Hence, this study aimed to explore the role of EphrinB2/EphB4 and the potential therapeutic effect of EphrinB2-Fc in the coronary arterial endothelial injury of KD. The levels of EphB4 were compared between KD patients and healthy children. Human coronary artery endothelial cells (HCAECs) were stimulated with sera from acute KD patients to establish the KD cell model. The overexpression of EphB4 or treatment with EphrinB2-Fc was found to intervene in the cell model. The cell migration, angiogenesis, and proliferation ability were assessed, and the expression of inflammation-related factors was measured. Our study showed that EphB4 showed low expression in both KD patients and the cell model of KD. The EphB4 protein levels in the CECs of CAA+ KD patients were much lower than those in healthy children. EphrinB2-Fc treatment of KD sera-activated HCAECs suppressed cell proliferation, reduced the expression of inflammation-related factors (such as IL-6 and P-selectin), and elevated cell angiogenesis ability. The results reveal that EphrinB2-Fc has a protective function in endothelial cells and has promising clinical applications for protecting vascular endothelium in patients with KD.
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