层粘连蛋白α2，α4和α5链正向调节少突胶质前体细胞的迁移和存活。,Scientific Reports

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层粘连蛋白α2，α4和α5链正向调节少突胶质前体细胞的迁移和存活。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-12-27 , DOI: 10.1038/s41598-019-56488-7
Nobuharu Suzuki _{1,

2} , Mai Hyodo ₂ , Chikako Hayashi _{1,

2} , Yo Mabuchi _{2,

3} , Kaori Sekimoto ₂ , Chinami Onchi ₁ , Kiyotoshi Sekiguchi ₄ , Chihiro Akazawa _{2,

3}

Affiliation

在发育中的中枢神经系统（CNS）中，少突胶质前体细胞（OPC）沿血管迁移并广泛分布在CNS中。同时，OPCs需要来自细胞外微环境的生存因子。在其他组织中，层粘连蛋白（异源三聚体（αβγ）细胞外基质蛋白）可促进细胞迁移和存活。但是，层粘连蛋白在OPC发育中的表达模式和功能仍然知之甚少。在本研究中，我们首先研究了出生后鼠脑中层粘连蛋白α链的表达，该层粘连蛋白与诸如整合素之类的细胞表面受体结合。我们发现层粘连蛋白α1，α2，α4和α5链在血管周围表达，并且OPC附着了层粘连蛋白α链阳性血管。然后，我们使用重组层粘连蛋白E8（LME8s）评估了这些层粘连蛋白对OPC活性的影响，这些重组层粘连蛋白E8是层粘连蛋白同工型的最小活性片段。连接到LM211E8，LM411E8和LM511E8上的OPC通过整联蛋白β1分别包含层粘连蛋白α2，α4和α5。此外，这三个LME8促进了OPC的迁移，并且通过粘着斑激酶的激活，LM411E8或LM511E8上的OPC生存期得以延长。总之，我们的发现表明，表达在周围血管中的层粘连蛋白通过整联蛋白β1-FAK途径正向调节OPC的迁移和存活。这三个LME8促进了OPC的迁移，并且通过粘着斑激酶的激活，LM411E8或LM511E8上的OPC生存期得以延长。总之，我们的发现表明，表达在周围血管中的层粘连蛋白通过整联蛋白β1-FAK途径正向调节OPC的迁移和存活。这三个LME8促进了OPC的迁移，并且通过粘着斑激酶的激活，LM411E8或LM511E8上的OPC生存期得以延长。总之，我们的发现表明，表达在周围血管中的层粘连蛋白通过整联蛋白β1-FAK途径正向调节OPC的迁移和存活。

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Laminin α2, α4, and α5 Chains Positively Regulate Migration and Survival of Oligodendrocyte Precursor Cells.

In the developing central nervous system (CNS), oligodendrocyte precursor cells (OPCs) migrate along blood vessels and are widely distributed in the CNS. Meanwhile, OPCs require survival factors from the extracellular microenvironment. In other tissues, laminins, heterotrimetric (αβγ) extracellular matrix proteins, promote cell migration and survival. However, the expression pattern and functions of laminins in OPC development remain poorly understood. In the present study, we first investigated the expression of laminin α chains, which bind to cell surface receptors such as integrins, in the postnatal murine brain. We found that laminin α1, α2, α4, and α5 chains were expressed around blood vessels and OPCs attached the laminin α chain-positive vessels. We then evaluated the effect of these laminins on OPCs activity using recombinant laminin E8s (LME8s) that are minimally active fragments of the laminin isoforms. OPCs attached on LM211E8, LM411E8, and LM511E8, containing laminin α2, α4, and α5 chains, respectively, through integrin β1. Further, these three LME8s promoted migration of OPCs, and OPC survival was prolonged on either LM411E8 or LM511E8 via the activation of focal adhesion kinase. Together, our findings suggest that laminins expressed surrounding blood vessels positively regulate migration and survival of OPCs through the integrin β1-FAK pathway.

更新日期：2019-12-27

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