氯化钆对人脐静脉内皮细胞体外血管形成能力的影响

doi:10.5246/jcps.2013.01.009

氯化钆对人脐静脉内皮细胞体外血管形成能力的影响

万箫, 苟宝迪^*, 王夔^*

北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2012-08-08 修回日期:2012-11-03 出版日期:2013-01-20 发布日期:2013-01-20
通讯作者: 苟宝迪*, 王夔*

Gadolinium-promoted angiogenesis involves the activation of PKCα/β2 and MAPKs in human umbilical vein endothelial cells

Xiao Wan, Baodi Gou^*, Kui Wang^*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2012-08-08 Revised:2012-11-03 Online:2013-01-20 Published:2013-01-20
Contact: Baodi Gou*, Kui Wang*

摘要/Abstract

摘要： 钆离子的配合物作为核磁共振造影增强剂在临床诊断中得到广泛应用。晚期肾病患者多次大剂量使用钆造影剂后, 可能发生肾源性系统纤维化, 目前其确切机理还不清楚。我们考察了不同浓度的氯化钆对人脐静脉内皮细胞的迁移和成管能力的影响; 在鸡胚尿囊膜模型中, 10 μM氯化钆诱导生成更多的新生血管。这些实验结果表明氯化钆具有促进人脐静脉内皮细胞体外血管形成能力, 这种作用涉及细胞内活性氧物种和钙离子水平的变化, 以及PKCα/β₂ 和MAPKs信号通路的激活。该研究为探索钆造影剂和肾源性系统纤维化之间的关系提供了新线索。

关键词: 氯化钆, 血管生成, 活性氧物种, 信号通路, 人脐静脉内皮细胞

Abstract: Gadolinium has been widely used as a contrast agent for magnetic resonance imaging in clinical practice. Recently, it was reported that gadolinium is involved in nephrogenic systemic fibrosis, although the exact mechanism by which gadolinium triggers nephrogenic systemic fibrosis remains unclear. In this study, we show that gadolinium chloride (GdCl₃) induced human umbilical vein endothelial cells (HUVECs) to migrate in Matrigel and tubulogenesis during wound healing. Chick chorioallantoic membrane assay confirmed that GdCl₃ stimulates angiogenesis. Under the optimal angiogenic concentration of GdCl₃ (10 μM), intracellular calcium concentration and reactive oxygen species generation were elevated. Moreover, western blotting results indicate that in cells treated with GdCl₃, Ca²⁺-dependent PKCα/β₂ was phosphorylated, and MAPKs pathways were also activated. Taken together, GdCl₃ has a potential effect on angiogenesis in HUVECs, and the possible mechanisms may involve oxidative stress and calcium-related signaling pathways.

Key words: Gadolinium chloride, Angiogenesis, Reactive oxygen species, Signaling pathways, Human umbilical vein endothelial cells

中图分类号:

R915

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 20637010).
^*Corresponding author. Tel.: 86-10-82801539

万箫, 苟宝迪^*, 王夔^*. 氯化钆对人脐静脉内皮细胞体外血管形成能力的影响[J]. , DOI: 10.5246/jcps.2013.01.009.

Xiao Wan, Baodi Gou^*, Kui Wang^*. Gadolinium-promoted angiogenesis involves the activation of PKCα/β2 and MAPKs in human umbilical vein endothelial cells [J]. , DOI: 10.5246/jcps.2013.01.009.

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