VEGF通过调节黏着斑促进间充质干细胞的黏附及铺展  

Vascular Endothelial Growth Factor Promotes Mesenchymal Stem Cells Adhering and Spreading

作　　者：王惠荟[1] 吕静雅[1] 胡雅楠[1] 徐晓静[1] 张焕相[1] 

机构地区：[1]苏州大学医学部细胞生物学系,江苏省干细胞研究重点实验室,苏州215123

出　　处：《中国细胞生物学学报》2012年第10期967-975,共9页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30870642;No.31071220)资助项目~~

摘　　要：间充质干细胞(mesenchymal stem cells,MSCs)具有多向分化潜能并能在体外趋化剂或细胞因子的作用下进行定向迁移,体内移植后可趋向迁移至脑瘤病灶区。细胞黏附是细胞迁移的首要条件,了解细胞黏附及其调控有助于细胞迁移机制的研究。细胞黏附及铺展涉及到黏着斑(fo-cal adhesions,FAs)的动态变化以及细胞骨架的重排。细胞铺展面积在黏附过程中逐渐增大,黏附初期形成的小的黏着复合物逐渐成熟,聚集在一起形成较大的FAs。肌动蛋白(F-actin)聚集形成的螺线圈样微丝结构逐渐被应力纤维代替,细胞也由圆形变为具有极性的梭形或多角形。黏着斑激酶(focal adhesion kinase,FAK)和桩蛋白(paxillin)具有调节FAs聚合及骨架重排的作用,其中,Y397-FAK和Y31/Y118-paxillin的磷酸化活性在细胞铺展过程中不断变化。FAs组装时,Y397-FAK的磷酸化活性升高;FAs成熟后,Y397-FAK的磷酸化活性下降。活化的FAK能够磷酸化Y31/Y118-paxillin,激活的paxillin参与调节细胞骨架的形成和排列。血管内皮生长因子(vascular endothelial growth factor,VEGF)诱导的MSCs黏附过程中,细胞面积变大,完全铺展的时间缩短,黏着斑及细胞骨架的形成均提前。另外,VEGF诱导的细胞铺展过程中形成的FAs形态细长,数量较多。该研究表明,VEGF通过调节黏着斑和细胞骨架促进MSCs的黏附与铺展,提示VEGF可以通过调节黏着斑进而调控MSCs的定向迁移,为细胞迁移行为的研究提供理论基础。Mesenchymal stem cells （MSCs）, which have the pluripotent ability, can migrate directionally toward chemotactic agents and cytokines in vitro or show a tropism to injured brain or gliomas. Cell adhering is the fisrt step for cell migration and the understanding of cell adhesion could be helpful for the study of cell migration. The assembly and distribution of focal adhesions （FAs） and the arrangement of F-actin cytoskeletons are involved in the process of cell adhesion. With the plating time extended, the adhering cells became spreading and formed small focal complexes （FXs） to mature big FAs. F-actin assembled as circular bundles at the early stage and then formed stress fibres that made the cells possess polarity. The tyrosine phosphorylation activation of Y397-FAK and Y3 l/Y118-paxillin （both proteins could regulate the assembly of FAs and the arrangement of F-actin cytoskel- etons） changed during the spreading. The activation of Y397-FAK increased while the FAs were assembling; then the activation decreased when the FAs were mature. Activated FAK could phosphorylate Y3 l/Y118-paxillin which participates in regulating the remodelling of F-actin cytoskeleton. Under the treatment of VEGF, cells formed ad- hesions faster and were more spreading. The maturation of FAs and cytoskeletons needs less time. Otherwise, the FAs were slender and with more quantity. Collectively, these results demonstrated that VEGF could regulate MSCs adhesion and spreeding including the formation of FAs and the arrangement of F-actin cytoskeletons. This suggests that VEGF may regulate the migration of MSCs through modulating the FAs and cytoskeletons. And our research provides rationale for the study of cell migration.

关 键 词：间充质干细胞 VEGF 黏着斑 细胞黏附 细胞铺展 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]