Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis
|Author(s)||Bouvard Claire1, 2, 3, Galy-Fauroux Isabelle2, 4, Grelac Francoise1, 2, Carpentier Wassila5, Lokajczyk Anna2, 6, Gandrille Sophie2, 6, 7, Colliec-Jouault Sylvia8, Fischer Anne-Marie2, 4, 7, Helley Dominique2, 4, 7|
|Affiliation(s)||1 : INSERM, UMR S765, F-75006 Paris, France.
2 : Univ Paris 05, Sorbonne Paris Cite, F-75006 Paris, France.
3 : Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France.
4 : INSERM, UMR S970, F-75015 Paris, France.
5 : Univ Paris 04, Plateforme P3S, F-75013 Paris, France.
6 : INSERM, UMR S1140, F-75006 Paris, France.
7 : Hop Europeen Georges Pompidou, AP HP, F-75015 Paris, France.
8 : IFREMER, F-44300 Nantes, France.
|Source||Marine Drugs (1660-3397) (Mdpi Ag), 2015-12 , Vol. 13 , N. 12 , P. 7446-7462|
|WOS© Times Cited||13|
|Keyword(s)||fucoidan, angiogenesis, vasculogenesis, migration, signaling, transcriptomics|
|Abstract||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.|