VEGF Enhances the Migration of MSCs in Neural Differentiation by Regulating Focal Adhesion Turnover
VEGF Enhances the Migration of MSCs in Neural Differentiation by Regulating Focal Adhesion Turnover
复制标题
VEGF 通过调节局灶粘附周转增强 MSC 在神经分化中的迁移
DOI：
10.1002/jcp.24997
复制
发表时间：
2015-11
影响因子：
5.6
通讯作者：
Zhang Huanxiang
中科院分区：
文献类型：
--
作者：
Wang Huihui;Wang Xingkai;Qu Jing;Yue Qing;Hu Ya'nan;Zhang Huanxiang
骨髓间充质干细胞（MSCs）由于其内在的神经元潜能和对受损神经组织的迁移性，在神经再生方面具有巨大的前景。然而，介导MSC迁移的趋化信号仍然知之甚少。在这里，我们研究了黏着斑激酶（FAK）和Rac 1在血管内皮生长因子（VEGF）刺激的MSC迁移神经分化中的调节作用。我们发现，不同分化状态的MSCs对VEGF的趋化反应存在显著差异，诱导前24 h的细胞迁移速度和效率最高。FAK作为下游信号分子，通过调节黏着斑（focal adhesion，FAs）的组装和分布以及F‐actin的重组，参与VEGF诱导的细胞迁移。骨髓间充质干细胞的神经分化状态与其细胞骨架和脂肪酸的特性及板状伪足形成能力密切相关。VEGF促进FA形成，FA分布不对称，并以时间依赖性方式诱导未分化和预诱导24 h的MSC的Y397-FAK和Y31/118-桩蛋白活化。PF-228或表达FAK-Y397 F突变体对FAK的抑制会损害VEGF诱导迁移期间MSC中FA的动力学。此外，Rac 1以FAK依赖性方式调节FA形成。Rac 1组成性激活突变体的过表达增加了未分化和24 h预诱导MSC中FA的数量，而PF-228抑制FAK可降低VEGF诱导的FA形成增加。总的来说，这些结果表明，FAK和Rac 1信号转导协调调节在VEGF诱导的MSC在不同的神经分化状态迁移的FA的动力学。J.细胞。Physiol.9999：2728-2742，2015。© 2015威利期刊公司.
Mesenchymal stem cells (MSCs) hold great promise in neural regeneration, due to their intrinsic neuronal potential and migratory tropism to damaged nervous tissues. However, the chemotactic signals mediating the migration of MSCs remain poorly understood. Here, we investigated the regulatory roles for focal adhesion kinase (FAK) and Rac1 in vascular endothelial growth factor (VEGF)‐stimulated migration of MSCs in neural differentiation. We found that MSCs in various differentiation states show significant different chemotactic responses to VEGF and cells in 24‐h preinduction state possess the highest migration speed and efficiency. FAK, as the downstream signaling molecule, is involved in the VEGF‐induced migration by regulating the assembly and distribution of focal adhesions (FAs) and reorganization of F‐actin. The features of FAs and cytoskeletons and the ability of lamellipodia formation are closely related to the neural differentiation states of MSCs. VEGF promotes FA formation with an asymmetric distribution of FAs and induces the activation of Y397‐FAK and Y31/118‐paxillin of undifferentiated and 24‐h preinduced MSCs in a time‐dependent manner. Inhibition of FAK by PF‐228 or expressing FAK‐Y397F mutant impairs the dynamics of FAs in MSCs during VEGF‐induced migration. Furthermore, Rac1 regulates FA formation in a FAK‐dependent manner. Overexpression of constitutive activated mutants of Rac1 increases the number of FAs in undifferentiated and 24‐h preinduced MSCs, while VEGF‐induced increase of FA formation is decreased by inhibiting FAK by PF‐228. Collectively, these results demonstrate that FAK and Rac1 signalings coordinately regulate the dynamics of FAs during VEGF‐induced migration of MSCs in varying neural differentiation states. J. Cell. Physiol. 9999: 2728–2742, 2015. © 2015 Wiley Periodicals, Inc.
登录
查看更多内容
影响因子：
11.2
作者：
Nakamizo, A;Marini, F;Lang, FF
通讯作者：
Lang, FF
影响因子：
4
作者：
Sarah E. Webb;Jeffrey W. Pollard;Gareth E. Jones
通讯作者：
Sarah E. Webb;Jeffrey W. Pollard;Gareth E. Jones
影响因子：
7.5
作者：
Tomar A;Schlaepfer DD
通讯作者：
Schlaepfer DD
影响因子：
3.3
作者：
Xiaoyun Xu;N. Geremia;F. Bao;A. Pniak;M. Rossoni;Arthur Brown
通讯作者：
Xiaoyun Xu;N. Geremia;F. Bao;A. Pniak;M. Rossoni;Arthur Brown
影响因子：
4
作者：
Alexanian, Arshak R.;Maiman, Dennis J.;Gennarelli, Thomas A.
通讯作者：
Gennarelli, Thomas A.