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Differentially expressed proteins underlying childhood cortical dysplasia with epilepsy identified by iTRAQ proteomic profiling

机译:通过iTRAQ蛋白质组学分析鉴定癫痫引起的儿童皮质发育异常的差异表达蛋白

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摘要

Cortical dysplasia accounts for at least 14% of epilepsy cases, and is mostly seen in children. However, the understanding of molecular mechanisms and pathogenesis underlying cortical dysplasia is limited. The aim of this cross-sectional study is to identify potential key molecules in the mechanisms of cortical dysplasia by screening the proteins expressed in brain tissues of childhood cortical dysplasia patients with epilepsy using isobaric tags for relative and absolute quantitation-based tandem mass spectrometry compared to controls, and several differentially expressed proteins that are not reported to be associated with cortical dysplasia previously were selected for validation using real-time polymerase chain reaction, immunoblotting and immunohistochemistry. 153 out of 3340 proteins were identified differentially expressed between childhood cortical dysplasia patients and controls. And FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, and FABP3 were selected for validation and identified to be increased in childhood cortical dysplasia patients, while PRDX6 and PSAP were identified decreased. This is the first report on differentially expressed proteins in childhood cortical dysplasia. We identified differential expression of FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, FABP3, PRDX6 and PSAP in childhood cortical dysplasia patients, these proteins are involved in various processes and have various function. These results may provide new directions or targets for the research of childhood cortical dysplasia, and may be helpful in revealing molecular mechanisms and pathogenesis and/or pathophysiology of childhood cortical dysplasia if further investigated.
机译:皮质发育异常至少占癫痫病例的14%,且多见于儿童。然而,对皮质发育异常的分子机制和发病机理的理解是有限的。这项横断面研究的目的是通过使用等压线标签基于相对定量和绝对定量串联质谱法,通过筛查癫痫病患儿的儿童皮质异型增生患者的脑组织中表达的蛋白质,来鉴定皮质异型增生机制中的潜在关键分子。使用实时聚合酶链反应,免疫印迹和免疫组化方法,选择对照和几种以前没有报道与皮质发育异常相关的差异表达蛋白进行验证。在3340种蛋白质中,有153种在儿童皮质发育不良患者和对照组之间差异表达。并选择FSCN1,CRMP1,NDRG1,DPYSL5,MAP4和FABP3进行验证,并确定其在儿童皮质发育不良患者中升高,而PRDX6和PSAP则下降。这是关于儿童皮质发育不良中差异表达的蛋白质的首次报道。我们确定了FSCN1,CRMP1,NDRG1,DPYSL5,MAP4,FABP3,PRDX6和PSAP在儿童皮质发育不良患者中的差异表达,这些蛋白参与各种过程,并具有各种功能。这些结果可能为儿童皮质发育不良研究提供新的方向或目标,如果进一步研究,可能有助于揭示儿童皮质发育异常的分子机制,发病机理和/或病理生理。

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