1. FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins
- Author
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Awan, Baarkullah, Turkov, David, Schumacher, Cameron, Jacobo, Antonio, McEnerney, Amber, Ramsey, Ashley, Xu, Gege, Park, Dayoung, Kalomoiris, Stefanos, Yao, Wei, Jao, Li-En, Allende, Miguel L, Lebrilla, Carlito B, and Fierro, Fernando A
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Stem Cell Research - Nonembryonic - Non-Human ,Stem Cell Research ,Biotechnology ,Animals ,Cell Movement ,Fibroblast Growth Factor 2 ,Gene Expression Profiling ,Gene Expression Regulation ,Glycosylation ,Humans ,Integrins ,Mesenchymal Stem Cells ,Mice ,Models ,Molecular ,Molecular Conformation ,Polysaccharides ,Structure-Activity Relationship ,FUT8 ,MSC ,core fucosylation ,mesenchymal stem cells ,migration ,multipotent stromal cells ,Clinical Sciences ,Biochemistry and cell biology - Abstract
Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical. We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits. Gain- and loss-of-function experiments show that FUT8 is both necessary and sufficient to induce migration of MSCs. Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model. Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position. Altogether, we show a mechanism whereby FGF2 promotes migration of MSCs by modifying N-glycans. This work may help improve delivery of MSCs in therapeutic settings.
- Published
- 2018