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富马酸二甲酯上调表皮神经嵴干细胞中主要神经营养因子的表达。

Dimethyl fumarate up-regulates expression of major neurotrophic factors in the epidermal neural crest stem cells.

作者信息

Salehi Mohammad Saied, Borhani-Haghighi Afshin, Pandamooz Sareh, Safari Anahid, Dargahi Leila, Dianatpour Mehdi, Tanideh Nader

机构信息

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Tissue Cell. 2019 Feb;56:114-120. doi: 10.1016/j.tice.2019.01.004. Epub 2019 Jan 25.

Abstract

There is an agreement that combining treatments can lead to substantial improvement, therefore the present study assessed the effects of different concentrations of dimethyl fumarate (DMF) on viability of epidermal neural crest stem cells (EPI-NCSCs). In addition, this investigation was designed to evaluate the effects of DMF on relative expression of major trophic factors mainly the ones with neurotrophic effects, expressed in EPI-NCSCs in order to enhance their therapeutic potential. To determine the appropriate concentration of DMF for EPI-NCSCs treatment, the MTT assay was employed and based on the obtained data, EPI-NCSCs treated with 10μM DMF for 6, 24, 72 or 168 h. In each time point, quantitative RT-PCR technique was used to evaluate NGF, NT-3, BDNF, GDNF and VEGF transcripts. The acquired data showed that 10μM DMF significantly increased the mRNA expression of NGF, NT-3 and BDNF, 72 h following treatment; however, DMF inhibitory effect on GDNF mRNA expression was observed in various time points. No significant changes were detected for VEGF transcript. Our findings reveled that expression of major neurotrophic factors were up-regulated by dimethyl fumarate treatment. Therefore, combining EPI-NCSCs with DMF treatment might be a valuable strategy to improve their therapeutic functions in vivo.

摘要

人们一致认为联合治疗可带来显著改善,因此本研究评估了不同浓度的富马酸二甲酯(DMF)对表皮神经嵴干细胞(EPI-NCSCs)活力的影响。此外,本研究旨在评估DMF对EPI-NCSCs中主要营养因子(主要是具有神经营养作用的因子)相对表达的影响,以增强其治疗潜力。为了确定用于EPI-NCSCs治疗的DMF合适浓度,采用了MTT试验,并根据获得的数据,用10μM DMF处理EPI-NCSCs 6、24、72或168小时。在每个时间点,使用定量RT-PCR技术评估NGF、NT-3、BDNF、GDNF和VEGF转录本。获得的数据表明,10μM DMF在处理72小时后显著增加了NGF、NT-3和BDNF的mRNA表达;然而,在不同时间点观察到DMF对GDNF mRNA表达有抑制作用。未检测到VEGF转录本有显著变化。我们的研究结果表明,富马酸二甲酯处理上调了主要神经营养因子的表达。因此,将EPI-NCSCs与DMF治疗相结合可能是提高其体内治疗功能的一种有价值的策略。

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