title: Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis.
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.
authors.affiliation: Inserm, UMR-S765, 75006 Paris, France. bouvard.claire@gmail.com.|Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. bouvard.claire@gmail.com.|Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France. bouvard.claire@gmail.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvard
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. isabelle.galy-fauroux@parisdescartes.fr.|Inserm, UMR-S970, 75015 Paris, France. isabelle.galy-fauroux@parisdescartes.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Galy-Fauroux
authors.affiliation: Inserm, UMR-S765, 75006 Paris, France. francoise.grelac@parisdescartes.fr.|Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. francoise.grelac@parisdescartes.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Grelac
authors.affiliation: Plateforme P3S, Sorbonne Universités, 75013 Paris, France. wassila.carpentier@upmc.fr.
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. anna.lokajczyk@parisdescartes.fr.|Inserm, UMR-S1140, 75006 Paris, France. anna.lokajczyk@parisdescartes.fr.
authors.forename: Anna
authors.initials: A
authors.lastname: Lokajczyk
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. sophie.gandrille@parisdescartes.fr.|Inserm, UMR-S1140, 75006 Paris, France. sophie.gandrille@parisdescartes.fr.|AP-HP, Hôpital Européen Georges Pompidou, 75015 Paris, France. sophie.gandrille@parisdescartes.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gandrille
authors.affiliation: IFREMER, Route de l'Ile d'Yeu, 44300 Nantes, France. sylvia.colliec.jouault@ifremer.fr.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Colliec-Jouault
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. anne-marie.fischer@egp.aphp.fr.|Inserm, UMR-S970, 75015 Paris, France. anne-marie.fischer@egp.aphp.fr.|AP-HP, Hôpital Européen Georges Pompidou, 75015 Paris, France. anne-marie.fischer@egp.aphp.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. dominique.helley@egp.aphp.fr.|Inserm, UMR-S970, 75015 Paris, France. dominique.helley@egp.aphp.fr.|AP-HP, Hôpital Européen Georges Pompidou, 75015 Paris, France. dominique.helley@egp.aphp.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Helley
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011134:Polysaccharides; D042461:Vascular Endothelial Growth Factor A; C007789:fucoidan; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: angiogenesis; fucoidan; migration; signaling; transcriptomics; vasculogenesis