Regulation of focal adhesion turnover in SDF-1α-stimulated migration of mesenchymal stem cells in neural differentiation
Regulation of focal adhesion turnover in SDF-1α-stimulated migration of mesenchymal stem cells in neural differentiation
复制标题
SDF-1α刺激间充质干细胞神经分化迁移中黏着斑周转的调节
DOI：
10.1038/s41598-017-09736-7
复制
发表时间：
2017-08-30
影响因子：
4.6
通讯作者：
Zhang, Huanxiang
中科院分区：
文献类型：
--
作者：
Hu, Ya'nan;Lu, Junhou;Zhang, Huanxiang
移植的间充质干细胞（MSCs）定向迁移到病变部位在细胞治疗的疗效中起着关键作用。我们之前的研究表明，在不同的神经分化状态下，MSCs对化学引诱剂具有不同的迁移能力。然而，潜在的机制尚未得到充分解决。在此，我们发现MSCs中局点粘连的组装和转换、FAK和paxillin的磷酸化以及F-actin的重组与它们响应SDF-1 α的分化状态密切相关。在SDF-1 α刺激后，FAs的周转速度更快，诱导前24小时的MSCs中FAs存在时间减少最明显，向SDF-1 α迁移最有效。此外，我们证实PI3K/Akt和MAPK通路参与SDF-1 α诱导的细胞迁移和FA组装的调控，并且其调控作用因分化状态的不同而有很大差异。综上所述，这些结果表明，在SDF-1 α的作用下，FA的组装和转换伴随着F-actin的重组，与MSCs的分化状态密切相关，这可能有助于这些细胞的不同趋化反应，从而有助于开发新的策略来提高MSCs治疗的疗效。
Directed migration of the transplanted mesenchymal stem cells ( MSCs) to the lesion sites plays a pivotal role in the efficacy of cell-based therapy. Our previous study demonstrates that MSCs under varying neural differentiation states possess different migratory capacities in response to chemoattractants. However, the underlying mechanism has not been fully addressed. Herein, we show that the assembly and turnover of focal adhesions, the phosphorylation of FAK and paxillin, and the reorganisation of F-actin in MSCs are closely related to their differentiation states in response to SDF-1 alpha. Upon SDF-1 alpha stimulation, FAs turnover more rapidly with the most obvious reduction in the existing time of FAs in MSCs of 24-h preinduction that exhibit the most effective migration towards SDF-1 alpha. Further, we confirm that PI3K/Akt and MAPK pathways participate in the regulation of SDF-1 alpha-induced cell migration and FA assembly, and moreover, that the regulatory effects vary greatly depending on the differentiation states. Collectively, these results demonstrate that FA assembly and turnover, which is accompanied with F-actin reorganisation in response to SDF-1 alpha, correlates closely with the differentiation states of MSCs, which might contribute to the different chemotactic responses of these cells, and thus help develop new strategy to improve the efficacy of MSCs-based therapy.