亚砷酸盐抑制血小板衍生生长因子受体-β介导的血管内皮细胞血管生成。

Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta.

作者信息

Wang Xiaotong, Mou Yan, Yue Zhen, Zhang Haiying, Su Xuejin, Wang Yang, Li Ronggui, Sun Xin

机构信息

Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.

Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China; The Second Hospital of Jilin University, Changchun, PR China.

出版信息

Environ Toxicol Pharmacol. 2016 Sep;46:168-173. doi: 10.1016/j.etap.2016.07.009. Epub 2016 Jul 18.

DOI:10.1016/j.etap.2016.07.009

PMID:27475902

Abstract

The present study aimed to investigate the effects of sodium arsenite (NaAsO2) on the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Firstly, a Matrigel-based in vitro angiogenesis assay demonstrated that arsenite suppressed the angiogenesis of HUVECs in a dose-dependent manner. Then by using a global inhibitor for multiple growth factor receptors (E7080) and a specific inhibitor of PDGFR-beta (CP-673451), we found that E7080 completely prevented and CP-673451 significantly decreased the angiogenesis of HUVECs. This suggested that angiogenesis of HUVECs depends on the signal pathway mediated by tyrosine kinase receptors and that among them, PDGFR-beta has an important regulatory function. Finally by using porcine aortic endothelial cells which stably express human PDGFR-beta, we found that arsenite suppressed the angiogenesis mediated by PDGFR-beta. Based on these results, we conclude that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism.

摘要

本研究旨在探讨亚砷酸钠（NaAsO₂）对人脐静脉内皮细胞（HUVECs）血管生成的影响及其相关机制。首先，基于基质胶的体外血管生成试验表明，亚砷酸盐以剂量依赖的方式抑制HUVECs的血管生成。然后，通过使用一种针对多种生长因子受体的全局抑制剂（E7080）和一种血小板衍生生长因子受体β（PDGFR-β）的特异性抑制剂（CP-673451），我们发现E7080完全阻止且CP-673451显著降低了HUVECs的血管生成。这表明HUVECs的血管生成依赖于酪氨酸激酶受体介导的信号通路，其中PDGFR-β具有重要的调节功能。最后，通过使用稳定表达人PDGFR-β的猪主动脉内皮细胞，我们发现亚砷酸盐抑制了由PDGFR-β介导的血管生成。基于这些结果，我们得出结论：亚砷酸盐抑制血管内皮细胞的血管生成，这种作用由PDGFR-β介导，并推测这可能是砷中毒时血管损伤的原因之一。