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使用血管内皮生长因子诱导的斑马鱼模型评估血管通透性的分子调控

Assessing Molecular Regulation of Vascular Permeability Using a VEGF-Inducible Zebrafish Model.

作者信息

Hoeppner Luke H

机构信息

The Hormel Institute, University of Minnesota, Austin, MN, USA.

Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.

出版信息

Methods Mol Biol. 2022;2475:339-350. doi: 10.1007/978-1-0716-2217-9_25.

DOI:10.1007/978-1-0716-2217-9_25
PMID:35451770
Abstract

Vascular endothelial growth factor (VEGF) stimulates vascular permeability in a variety of human pathologies, such as cancer, ischemic stroke, cardiovascular disease, retinal conditions, and COVID-19-associated pulmonary edema, sepsis, acute lung injury, and acute respiratory distress syndrome. Comprehensive investigation of the molecular mechanisms of VEGF-induced vascular permeability has been hindered by the lack of in vivo models that easily facilitate genetic manipulation studies in real time. To address this need, we generated a heat-inducible VEGF transgenic zebrafish model of vascular permeability. Here, we describe how this zebrafish model can be used to monitor VEGF-induced vascular permeability through live in vivo imaging to identify genetic regulators that play key roles in vascular barrier integrity in physiological conditions and human disease processes.

摘要

血管内皮生长因子(VEGF)在多种人类疾病中刺激血管通透性,如癌症、缺血性中风、心血管疾病、视网膜疾病以及与COVID-19相关的肺水肿、脓毒症、急性肺损伤和急性呼吸窘迫综合征。由于缺乏易于实时促进基因操作研究的体内模型,对VEGF诱导血管通透性的分子机制的全面研究受到了阻碍。为满足这一需求,我们构建了一种热诱导的VEGF转基因斑马鱼血管通透性模型。在此,我们描述了如何利用这种斑马鱼模型通过活体体内成像监测VEGF诱导的血管通透性,以识别在生理条件和人类疾病过程中对血管屏障完整性起关键作用的基因调节因子。

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本文引用的文献

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Zebrafish. 2018 Jun;15(3):295-309. doi: 10.1089/zeb.2017.1515. Epub 2018 Feb 27.
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Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies.探寻治愈方法:利用斑马鱼开发精准肿瘤学疗法的魅力
NPJ Precis Oncol. 2017;1. doi: 10.1038/s41698-017-0043-9. Epub 2017 Nov 27.
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Guidelines for morpholino use in zebrafish.斑马鱼中吗啉代使用指南。
PLoS Genet. 2017 Oct 19;13(10):e1007000. doi: 10.1371/journal.pgen.1007000. eCollection 2017 Oct.
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Breeding Zebrafish: A Review of Different Methods and a Discussion on Standardization.斑马鱼养殖:不同方法综述及标准化探讨
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RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells.RhoC通过调节内皮细胞中VEGF诱导的信号传导来维持血管稳态。
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