Effects of Vitamin A and D on DNA Methyltransferases 3A and 3B Expression and Neural Stem Cell Differentiation

P. Mokarram, Parisa Alizadeh, S. Saeb, Nasim Rahmani-Kukia, M. Babazadeh, M. Siri
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Abstract

Background: In Multiple Sclerosis (MS) as the demyelination happens, Oligodendrocyte Precursor Cells (OPCs) migrate to the site of injury and start differentiating into mature oligodendrocytes to regenerate the myelin sheaths. This OPC differentiation process can be affected by the epigenetic mechanisms which are mediated by a family of DNA methyltransferases (DNMTs) such as DNMT3A and DNMT3B. However, Dietary factors can alter the DNMTs expressions and even their activities. Therefore, in this study the effect of dietary factors such as vitamin A and D on the expression of DNMT3A and DNMT3B genes was assessed during these cells. Methods: Rat embryonic stem cells were derived from ganglionic eminence. Then, the stem cells were cultured, differentiated and divided into five groups: control negative, control positive and three treatment modalities consist of vitamin D3, vitamin A, and vitamin A+D. Lastly, the Real-time PCR assay was conducted with total RNA. Results: The expression of DNMT3B gene was significantly different between the groups, especially in the groups treated with vitamin A. Conclusion: It seems that vitamin A can affect the expression of DNMT3B which plays a major role in cell differentiation and can be considered as a novel target for treatment of MS disease.
维生素A和D对DNA甲基转移酶3A和3B表达及神经干细胞分化的影响
背景:在多发性硬化症(MS)中,随着脱髓鞘的发生,少突胶质前体细胞(OPCs)迁移到损伤部位并开始分化为成熟的少突胶质细胞以再生髓鞘。这种OPC分化过程可能受到表观遗传机制的影响,该机制是由DNA甲基转移酶(DNMT3A和DNMT3B)家族介导的。然而,饮食因素可以改变dnmt的表达甚至活性。因此,本研究评估了维生素A和D等膳食因子对这些细胞中DNMT3A和DNMT3B基因表达的影响。方法:从大鼠神经节隆起处提取胚胎干细胞。然后对干细胞进行培养、分化,分为对照阴性组、对照阳性组和维生素D3、维生素A、维生素A+D三种处理方式。最后,用总RNA进行Real-time PCR检测。结果:各组间DNMT3B基因表达差异显著,尤其是维生素A组。结论:维生素A似乎可以影响DNMT3B的表达,而DNMT3B在细胞分化中起着重要作用,可以考虑作为治疗MS疾病的新靶点。
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