Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric Epileptic Patients.
Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric Epileptic Patients.
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丙戊酸（VPA）在小儿癫痫患者中诱导的差异基因表达谱。
DOI：
10.3390/genes9070328
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发表时间：
2018-06-28
期刊：
影响因子：
3.5
通讯作者：
Cárdenas-Rodríguez N
中科院分区：
文献类型：
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作者：
Floriano-Sánchez E;Brindis F;Ortega-Cuellar D;Ignacio-Mejía I;Moreno-Arriola E;Romero-Morelos P;Ceballos-Vasquez E;Córdova-Espinoza MG;Arregoitia-Sarabia CK;Sandoval-Pacheco R;Carmona-Aparicio L;Cárdenas-Rodríguez N
癫痫是一种神经元疾病，影响全球多达7000万人。有效治疗儿童癫痫的发展需要早期生物标志物。在这里，我们在血细胞中进行了全基因组微阵列分析，以确定癫痫和癫痫丙戊酸（VPA）治疗的儿童与正常儿童之间差异表达的基因，以获得有关基因表达的信息，以帮助我们了解这种疾病的遗传方面。我们发现，最显著的差异表达基因与转录因子cAMP反应元件结合蛋白（CREB）有关，与正常儿童相比，癫痫儿童中CREB过表达，6个月和12个月的VPA治疗逆转了其中一些变化。有趣的是，白细胞相关免疫球蛋白样受体1（LAIR 1），一种结合胶原蛋白并含有CREB结合位点的I型跨膜糖蛋白，是癫痫患者中上调较多的基因之一，VPA治疗强烈逆转了其上调。CREB上调与癫痫相关的基因;在这里，我们认为LAIR 1可以激活CREB，它们一起触发癫痫。VPA治疗后，LAIR 1通过破坏功能性LAIR 1-CREB复合物抑制基因，导致治疗成功。功能性微阵列分析提供了新的信息，可以开辟新的研究途径，在生物标志物的发现，这可能是有用的早期识别儿童与癫痫的易感性。
Epilepsy is a neuronal disease that affects up to 70 million people worldwide. The development of effective therapies to combat childhood epilepsy requires early biomarkers. Here, we performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between epileptic and epileptic valproic acid (VPA)-treated children versus normal children to obtain information about the gene expression to help us to understand genetic aspects of this disease. We found that the most significant differentially expressed genes were related to the transcriptional factor cAMP-response element binding protein (CREB) that is overexpressed in children with epilepsy compared with normal children, and 6 and 12 months of VPA treatment reversed several of these changes. Interestingly, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), a type I transmembrane glycoprotein that binds collagen proteins and contains CREB binding sites, was one of the more up-regulated genes in epileptic patients, and treatment with VPA strongly reversed its up-regulation. CREB up-regulates genes related to epilepsy; here, we suggest that LAIR1 could activate CREB, and together, they trigger epilepsy. After VPA treatment, LAIR1 repressed genes by disrupting the functional LAIR1–CREB complex, resulting in successful treatment. A functional microarray analysis offers new information that could open novel avenues of research in biomarker discovery, which may be useful for the early identification of children with a predisposition to epilepsy.
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影响因子：
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作者：
Cárdenas-Rodríguez N;Coballase-Urrutia E;Pérez-Cruz C;Montesinos-Correa H;Rivera-Espinosa L;Sampieri A 3rd;Carmona-Aparicio L
通讯作者：
Carmona-Aparicio L
影响因子：
5.1
作者：
Borlikova, Gilyana;Endo, Shogo
通讯作者：
Endo, Shogo
影响因子：
5.6
作者：
Cardenas-Rodriguez N;Huerta-Gertrudis B;Rivera-Espinosa L;Montesinos-Correa H;Bandala C;Carmona-Aparicio L;Coballase-Urrutia E
通讯作者：
Coballase-Urrutia E
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1002/bdra.23458
发表时间：
2016-01-01
影响因子：
--
作者：
Krutzke, Sophia K.;Engels, Hartmut;Merz, Waltraut M.
通讯作者：
Merz, Waltraut M.