Functional evaluation of TIE2 activators identified in a model system using human umbilical vein endothelial cells

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-06-15 DOI:10.1016/j.bmcl.2025.130311

Saki Igarashi , Koki Ishigami , Naonori Uchida , Eisuke Kato

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Abstract

TIE2 (or TEK) receptor is a tyrosine kinase receptor important for maintaining vascular system function. Decreased TIE2 signalling associates with various diseases and deletion of TIE2 increases the risk of vascular diseases like atherosclerosis. Therefore, activators of TIE2 are suggested and shown to be efficient for maintaining healthy vascular systems and protect from diseases. We have previously explored several plant derived compounds as TIE2 activator using transiently expressed TIE2 in HeLa cells. In this study, we evaluated if the identified TIE2 activators, casuarinin, procyanidin tetramer (PC4), and morin, are capable to activate TIE2 signalling in human umbilical vein endothelial cells. We showed that casuarinin and PC4 activates AKT and ERK, the two kinase downstream of TIE2, and enhances tube formation in human umbilical vein endothelial cells. These results support the idea that the TIE2 activators identified in the TIE2-expressing HeLa cells are candidates for vascular protection.

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在人脐静脉内皮细胞模型系统中鉴定的TIE2激活剂的功能评估。

TIE2（或TEK）受体是维持血管系统功能的重要酪氨酸激酶受体。TIE2信号的减少与多种疾病有关，而TIE2的缺失增加了动脉粥样硬化等血管疾病的风险。因此，TIE2的激活剂被认为对维持健康的血管系统和预防疾病是有效的。我们之前已经在HeLa细胞中利用瞬时表达的TIE2探索了几种植物源化合物作为TIE2激活剂。在这项研究中，我们评估了鉴定出的TIE2激活剂木麻黄素、原花青素四聚体（PC4）和桑辣素是否能够激活人脐静脉内皮细胞中的TIE2信号。我们发现，木麻黄素和PC4可以激活TIE2下游的AKT和ERK激酶，并促进人脐静脉内皮细胞的管状形成。这些结果支持了在表达TIE2的HeLa细胞中发现的TIE2激活剂是血管保护的候选者的观点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.