He Xiu-Ying, Dan Qi-Qin, Wang Fang, Li Yu-Kai, Fu Song-Jun, Zhao Nan, Wang Ting-Hua
Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
Institute of Neuroscience, Laboratory Zoology Department, Kunming Medical University, Kunming, China.
Front Neurosci. 2019 Jan 31;12:1049. doi: 10.3389/fnins.2018.01049. eCollection 2018.
Traumatic brain injury (TBI) often leads to severe neurobehavioral impairment, but the underlying molecular mechanism remains to be elucidated. Here, we collected the sera from 23 patients (aged from 19 to 81 years old, third day after TBI as TBI-third group) subjected to TBI from The First Hospital of Kunming City, and the sera from 22 healthy donors (aged from 18 to 81 years old and as control group). Then, three samples from TBI-third group and three samples from control group were subjected to the protein microarray detection, and bioinformatics analysis. Then, enzyme-linked immunosorbent assay (ELISA) was used to verify significantly altered protein levels. Results showed that, when compared with the control group, all significantly differentially expressed proteins [DEPs, < 0.05, FDR < 0.05, fold change (FC) > 2] contained 172 molecules in the TBI-third group, in which 65 proteins were upregulated, while 107 proteins were downregulated. The biological processes of these DEPs, mostly happened in the extracellular region and the extracellular region parts, are mainly involved in the regulation of cellular process, signaling and signal transduction, cell communication, response to stimuli, the immune system process and multicellular organismal development. Moreover, the essential molecular functions of them are cytokine activity, growth factor activity and morphogen activity. Additionally, the most significant pathways are enriched in cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways among downregulated proteins, and pathways in cancer and cytokine-cytokine receptor interaction among upregulated proteins. Of these, we focused on the NGF, NT-3, IGF-2, HGF, NPY, CRP, MMP-9, and ICAM-2 with a high number of interactors in Protein-Protein Interaction (PPI) Network indicated by bioinformatics report. Furthermore, using ELISA test, we confirmed that all increase in the levels of NGF, NT-3, IGF-2, HGF, NPY, CRP, MMP-9, and ICAM-2 in the serum from TBI patients. Together, we determined the screened protein expressional profiles in serum for TBI patients, in which the cross-network between inflammatory factors and growth factors may play a crucial role in TBI damage and repair. Our findings could contribute to indication for the diagnosis and treatment of TBI in future translational medicine and clinical practice.
创伤性脑损伤（TBI）常导致严重的神经行为障碍，但其潜在的分子机制仍有待阐明。在此，我们收集了昆明市第一医院23例TBI患者（年龄19至81岁，TBI后第三天作为TBI - 第三组）的血清，以及22例健康供者（年龄18至81岁，作为对照组）的血清。然后，对TBI - 第三组的3个样本和对照组的3个样本进行蛋白质微阵列检测及生物信息学分析。接着，采用酶联免疫吸附测定（ELISA）来验证显著改变的蛋白质水平。结果显示，与对照组相比，TBI - 第三组中所有显著差异表达蛋白[DEPs，< 0.05，FDR < 0.05，变化倍数（FC）> 2]包含172个分子，其中65种蛋白质上调，107种蛋白质下调。这些DEPs的生物学过程大多发生在细胞外区域及细胞外区域部分，主要涉及细胞过程调控、信号传导与信号转导、细胞通讯、对刺激的反应、免疫系统过程以及多细胞生物体发育。此外，它们的基本分子功能为细胞因子活性、生长因子活性和形态发生素活性。另外，下调蛋白中最显著富集的通路为细胞因子 - 细胞因子受体相互作用和PI3K - Akt信号通路，上调蛋白中为癌症通路和细胞因子 - 细胞因子受体相互作用。其中，我们关注了生物信息学报告显示在蛋白质 - 蛋白质相互作用（PPI）网络中有大量相互作用分子的NGF、NT - 3、IGF - 2、HGF、NPY、CRP、MMP - 9和ICAM - 2。此外，通过ELISA检测，我们证实了TBI患者血清中NGF、NT - 3、IGF - 2、HGF、NPY、CRP、MMP - 9和ICAM - 2的水平均升高。总之，我们确定了TBI患者血清中的筛选蛋白表达谱，其中炎症因子和生长因子之间的交叉网络可能在TBI损伤和修复中起关键作用。我们的研究结果可能有助于未来转化医学和临床实践中TBI诊断和治疗的指征。
