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首页> 外文期刊>International journal of molecular medicine >Effects of histone deacetylase inhibition on the survival, proliferation and migration of Schwann cells, as well as on the expression of neurotrophic factors and genes associated with myelination
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Effects of histone deacetylase inhibition on the survival, proliferation and migration of Schwann cells, as well as on the expression of neurotrophic factors and genes associated with myelination

机译:组蛋白脱乙酰基酶抑制对雪旺细胞存活,增殖和迁移以及神经营养因子和与髓鞘形成有关的基因表达的影响

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Trichostatin A?(TSA), a histone deacetylase?(HDAC) inhibitor, has been shown to have neuroprotective, neurotrophic and anti-inflammatory properties in both animal and cellular models of neurodegenerative disorders. In a previous study of ours, we demonstrated that TSA inhibited the proliferation and increased the differentiation of neuronal precursor cells?(NPCs). However, the effects of TSA on Schwann cells?(SCs) have not yet been fully elucidated. Thus, in the present study, using SCs derived from adult rat sciatic nerves, we investigated the effects of TSA on the survival, proliferation, migration and myelination of SCs. We found that TSA significantly induced SC death when used at high concentrations. We also observed that TSA promoted the proliferation of SCs in a time-dependent manner. In addition, TSA inhibited the migration of SCs. Moreover, RT-PCR revealed that TSA increased the mRNA expression of several neurotrophic factors and inhibited the expression of genes associated with myelination, including myelin basic protein?(MBP) and myelin protein zero?(MPZ). Taken together, our results suggest that TSA plays an important role in regulating the growth and biological function of SCs. These data may contribute to our understanding of TSA-based treatment of neurodegenerative diseases.
机译:组蛋白脱乙酰基酶(HDAC)抑制剂曲古他汀A(TSA)在神经退行性疾病的动物和细胞模型中均具有神经保护,神经营养和抗炎特性。在我们之前的研究中,我们证明了TSA抑制神经元前体细胞(NPC)的增殖并增加其分化。但是,尚未完全阐明TSA对雪旺细胞(SCs)的作用。因此,在本研究中,我们使用源自成年大鼠坐骨神经的SC​​,研究了TSA对SC存活,增殖,迁移和髓鞘形成的影响。我们发现,高浓度使用TSA时,可显着诱导SC死亡。我们还观察到,TSA以时间依赖性方式促进了SC的增殖。此外,TSA抑制了SC的迁移。此外,RT-PCR显示TSA增加了几种神经营养因子的mRNA表达,并抑制了与髓鞘形成有关的基因的表达,包括髓鞘碱性蛋白?(MBP)和髓鞘蛋白零?(MPZ)。综上所述,我们的结果表明,TSA在调节SC的生长和生物学功能中起着重要作用。这些数据可能有助于我们了解基于TSA的神经退行性疾病的治疗方法。

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