β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain.
β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain.
复制标题
DOI：
10.1016/j.ebiom.2017.01.005
复制
发表时间：
2017-02
期刊：
影响因子：
11.1
通讯作者：
Sawamoto K
中科院分区：
文献类型：
--
作者：
Fujioka T;Kaneko N;Ajioka I;Nakaguchi K;Omata T;Ohba H;Fässler R;García-Verdugo JM;Sekiguchi K;Matsukawa N;Sawamoto K
缺血性脑卒中是导致慢性残疾的主要原因。然而，目前还没有有效的治疗方法来促进中风引起的神经系统症状的恢复。最近的研究表明，中风后，未成熟的神经元，称为神经母细胞，产生于神经原生态位，脑室-脑室下区，迁移到受伤的区域，在那里他们分化成成熟的神经元。增加分布在病变处和周围的神经母细胞数量的干预措施有助于缺血性卒中啮齿动物模型中的神经元修复，这表明促进卒中后脑中的神经母细胞迁移可以提高有效的神经元再生。为了向病变移动，神经母细胞形成链状聚集体并沿沿着迁移，这被认为增加了它们的迁移效率。然而，调节这些迁移过程的分子机制在很大程度上是未知的。在这里，我们研究了β1类整合素，细胞外基质蛋白的跨膜受体，在这些迁移的成神经细胞中的作用。我们发现，神经母细胞链的形成和血管引导的迁移关键取决于β1整合素信号。β1整合素促进成神经细胞与层粘连蛋白的粘附，促进成神经细胞迁移过程中索马体的有效移位。此外，含层粘连蛋白的人工支架促进了成神经细胞链的形成和向损伤区域的迁移。这些数据表明，通过β1整合素的层粘连蛋白信号支持血管引导的神经元迁移，以有效地向损伤区域提供成神经细胞。这项研究还强调了血管支架在发育和再生中细胞迁移的重要性。β1类整合素促进损伤脑中血管引导的神经元迁移β1类整合素诱导层粘连蛋白依赖的神经元粘附和染色体易位。含层粘连蛋白的人工支架促进神经元迁移。虽然中风是慢性残疾的主要原因，但目前还没有有效的治疗方法来促进中风后的恢复。最近的研究表明，在中风后的大脑中，脑室壁中产生的未成熟神经元迁移并分化为成熟神经元，以在功能上取代受损的神经元。Fujioka等证明，在未成熟神经元中表达的β1类整联蛋白使其能够沿血管沿着迁移，有助于小鼠中风后的神经元再生。此外，含有层粘连蛋白的支架促进了培养物和损伤脑组织中的神经元迁移。这些发现阐明了血管作为细胞迁移和再生支架的作用。
Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration. β1-class integrins facilitate blood vessel-guided neuronal migration in injured brain. β1-class integrins induce laminin-dependent neuronal adhesion and somal translocation. Laminin-containing artificial scaffolds promote neuronal migration. Although stroke is a major cause of chronic disability, there are presently no effective treatments for promoting recovery after stroke. Recent studies suggest that in the post-stroke brain, immature neurons generated in brain ventricle walls migrate and differentiate into mature neurons to functionally replace damaged neurons. Fujioka et al. demonstrate that β1-class integrins expressed in immature neurons enable their migration along blood vessels, contributing to neuronal regeneration after stroke in mice. Furthermore, laminin-containing scaffolds promoted neuronal migration in culture and in injured brain tissue. These findings elucidate the role of blood vessels as a scaffold for cell migration and regeneration.