Orexin-A Attenuates Inflammatory Responses in Lipopolysaccharide-Induced Neural Stem Cells by Regulating NF-KB and Phosphorylation of MAPK/P38/Erk Pathways.
Orexin-A Attenuates Inflammatory Responses in Lipopolysaccharide-Induced Neural Stem Cells by Regulating NF-KB and Phosphorylation of MAPK/P38/Erk Pathways.
复制标题
DOI：
10.2147/jir.s308078
复制
发表时间：
2021
影响因子：
4.5
通讯作者：
Feng Z
中科院分区：
文献类型：
--
作者：
Ye W;Yan Y;Tang Y;Dong X;Chen G;Kang J;Huang L;Xiong Q;Feng Z
神经元损伤是神经系统疾病的主要原因。神经干细胞（Neural Stem Cells，NSCs）具有神经元的细胞修复和替代、神经营养因子的分泌以及神经微环境的免疫调节等功能。以往的研究发现Orexin-A对中枢神经系统的神经元具有保护作用，但对Orexin-A对神经干细胞的作用研究较少。本研究旨在探讨Orexin-A对脂多糖（lipopolysaccharide，LPS）诱导的神经干细胞的抗炎作用及其信号转导机制。实时定量聚合酶链反应检测mRNA水平。Western blot检测细胞内信号通路相关蛋白的表达。采用CCK-8检测试剂盒和transwell法检测神经干细胞的增殖和迁移。HE染色观察细胞形态。Orexin-A通过调节核因子-k-基因结合（NF-kB）和P38/ERK-丝裂原活化蛋白激酶（MAPK）通路的磷酸化而不是p-JNK信号通路，降低LPS诱导的促炎细胞因子IL-1β、TNF-α和IL-6。我们的研究结果表明Orexin-A可以减轻NSC的炎症反应。它可以为神经干细胞治疗应用提供有益的帮助。
Neuronal damage is the main cause of neurological diseases. Neural stem cells (NSCs) have the functions of cell repair and replacement of neurons, secretion of neurotrophic factors, and immune regulation of the neural microenvironment. Previous study found that Orexin-A had a protective effect on neurons in the central nervous system, but it is lacking in making great efforts on the function of Orexin-A on NSCs. This study aimed to investigate the anti-inflammatory responses and signaling mechanisms of Orexin-A on lipopolysaccharide (LPS)-induced NSCs. Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Signaling pathway-related protein expression was detected by Western blot. The proliferation and migration of NSCs were investigated by Cell Counting Kit-8 (CCK-8) detection kit and transwell assay. Besides, the staining of hematoxylin and eosin (HE) was performed to study the morphology of cell. Orexin-A decreased the pro-inflammatory cytokines of IL-1β, TNF-α, and IL-6 induced by LPS by regulating nuclear factor-k-gene binding (NF-kB) and phosphorylation of P38/Erk-mitogen-activated protein kinases (MAPKs) pathways, but not p-JNK signaling. Our findings indicate that Orexin-A can alleviate the inflammatory response of NSC. It can provide beneficial help in neural stem cell therapy applications.