Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro,Journal of Neurochemistry

当前位置： X-MOL 学术 › J. Neurochem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-10-28 , DOI: 10.1111/jnc.15225
Fayi Nie ₁ , Qiaoxia Zhang ₁ , Jie Ma _{1,

2} , Pengjie Wang ₁ , Ruiying Gu ₁ , Jing Han ₁ , Rui Zhang ₃

Affiliation

Schizophrenia is a severe psychiatric disorder with a strong hereditary component that affects approximately 1% of the world's population. The disease is most likely caused by the altered expression of a number of genes that function at the level of biological pathways or gene networks. Transcription factors (TF) are indispensable regulators of gene expression. EGR3 is a TF associated with schizophrenia. In the current study, DNA microarray and ingenuity pathway analyses (IPA) demonstrated that EGR3 regulates Reelin signaling pathway in SH-SY5Y cells. ChIP and luciferase reporter studies confirmed that EGR3 directly binds to the promoter region of RELN thereby activating RELN expression. The expression of both EGR3 and RELN was decreased during neuronal differentiation induced by retinoic acid (RA) in SH-SY5Y cells, and EGR3 over-expression reduced neurite outgrowth which could be partially reversed by the knockdown of RELN. The expression levels of EGR3 and RELN in peripheral blood of subjects with schizophrenia were found to be down-regulated (compared with healthy controls), and were positively correlated. Furthermore, data mining from public databases revealed that the expression levels of EGR3 and RELN were presented a positive correlation in post-mortem brain tissue of subjects with schizophrenia. Taken together, this study suggests that EGR3 is a novel TF of the RELN gene and regulates neurite outgrowth via the Reelin signaling pathway. Our findings contribute to the understanding of the regulatory role of EGR3 in the pathophysiology and molecular mechanisms of schizophrenia, and potentially to the development of new therapies and diagnostic biomarkers for the disorder.

中文翻译：

精神分裂症风险候选者 EGR3 是一种新型的 RELN 转录调节因子，并通过体外 Reelin 信号通路调节神经突生长

精神分裂症是一种严重的精神疾病，具有很强的遗传性，影响着世界上大约 1% 的人口。这种疾病很可能是由许多在生物途径或基因网络水平上发挥作用的基因的表达改变引起的。转录因子 (TF) 是基因表达不可或缺的调节因子。EGR3 是与精神分裂症相关的 TF。在当前的研究中，DNA 微阵列和独创性通路分析 (IPA) 表明 EGR3 调节 SH-SY5Y 细胞中的 Reelin 信号通路。ChIP 和荧光素酶报告基因研究证实，EGR3 直接结合RELN的启动子区域，从而激活RELN表达。EGR3和RELN的表达在 SH-SY5Y 细胞中由视黄酸 (RA) 诱导的神经元分化过程中，EGR3 的过表达减少了神经突的生长，这可以通过RELN的敲低来部分逆转。发现精神分裂症患者外周血中EGR3和RELN的表达水平被下调（与健康对照相比），并且呈正相关。此外，公共数据库的数据挖掘显示，EGR3和RELN的表达水平在精神分裂症受试者的死后脑组织中呈正相关。总之，这项研究表明 EGR3 是RELN 的一种新型 TF基因并通过 Reelin 信号通路调节神经突的生长。我们的研究结果有助于了解 EGR3 在精神分裂症的病理生理学和分子机制中的调节作用，并可能有助于开发该疾病的新疗法和诊断生物标志物。

更新日期：2020-10-28

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11