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FGF2 通过增加整合素 N-糖基化核心岩藻糖基化来诱导人骨髓基质细胞的迁移。

FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.

机构信息

Institute for Regenerative Cures, University of California, Davis, Sacramento, CA, USA.

Department of Chemistry, University of California, Davis, Davis, CA, USA.

出版信息

Stem Cell Reports. 2018 Aug 14;11(2):325-333. doi: 10.1016/j.stemcr.2018.06.007. Epub 2018 Jul 5.

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.

摘要

由于数百项临床试验正在研究多能基质细胞(MSCs)在治疗中的用途,因此将细胞有效递送到靶组织至关重要。我们发现了一种未被探索的机制,即碱性成纤维细胞生长因子(FGF2)诱导岩藻糖基转移酶 8(FUT8)的表达,从而增加包括几种整合素亚基在内的膜相关蛋白的 N 连接糖基的核心岩藻糖基化。功能获得和功能丧失实验表明,FUT8 既是诱导 MSC 迁移所必需的,也是充分的。沉默 FUT8 也会影响斑马鱼胚胎和小鼠骨折模型中 MSC 的迁移。最后,我们使用计算建模表明,核心岩藻糖基化限制了整合素表面糖基的自由度,从而稳定了特定位置上的糖基。总之,我们展示了一种机制,即 FGF2 通过修饰 N-糖基来促进 MSC 的迁移。这项工作可能有助于改善治疗环境中 MSC 的递送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b7/6093088/ad9553f2eed2/fx1.jpg

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