Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis.
Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis.
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DOI：
10.3390/md13127075
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发表时间：
2015-12-18
期刊：
影响因子：
5.4
通讯作者：
Helley D
中科院分区：
文献类型：
--
作者：
Bouvard C;Galy-Fauroux I;Grelac F;Carpentier W;Lokajczyk A;Gandrille S;Colliec-Jouault S;Fischer AM;Helley D
低分子量岩藻聚糖（LMWF）是从褐藻中提取的硫酸酸化多糖，具有抗血栓和促血管生成的特性。然而，其作用机制尚不清楚。本实验研究了低分子肝素对人脐静脉内皮细胞和内皮集落形成细胞信号传导和全基因组表达的影响。我们观察到LMWF和血管内皮生长因子对细胞信号传导具有协同作用，更有趣的是，在没有其他生长因子的情况下，LMWF本身能够触发PI3K/AKT通路的激活，该通路在血管生成和血管生成中起着至关重要的作用。我们还观察到LMWF对细胞迁移的影响是PI3K/ akt依赖性的，并且LMWF调节了参与不同水平的新血管形成过程的基因的表达，如细胞迁移和细胞骨架组织，细胞动员和归巢。这为LMWF的作用机制提供了更好的理解，并证实了它可能是一种有趣的血管修复治疗方法。
Low-molecular-weight fucoidan (LMWF) is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF’s mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair.