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Front. Neurosci. | doi: 10.3389/fnins.2018.01049

Protein network analysis of the serum and their functional implication in patients subjected to traumatic brain injury

 Xiu-Ying He1, 2, Qi-Qin Dan2, Fang Wang3, Yu-Kai Li3, Song-Jun Fu3,  Nan Zhao4* and  Ting-Hua Wang2, 3*
  • 1Sichuan University, China
  • 2Translational Neuroscience Center, West China Hospital, Sichuan University, China
  • 3Institute of Neuroscience, Kunming Medical University, China
  • 4Department of Neurosurgery, The First Hospital of Kunming, China

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, 3rd day after TBI as TBI-3rd 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-3rd 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 control group, all significantly differentially expressed protein (DEPs, P < 0.05, FDR< 0.05, fold change (FC) > 2) contained 172 molecules in the TBI-3rd group, in which 65 proteins were upregulated, while 107 proteins were downregulated. The biological processes of these DEPs, mostly happened in extracellular region and extracellular region part, are mainly involved in regulation of cellular process, signaling and signal transduction, cell communication, response to stimulus, 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 pathway 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 the high number of interactors in Protein-Protein Interaction (PPI) Network indicated by bioinformatics report. Furthermore, using ELISA test, we confirmed all increase in the level 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.

Keywords: protein network analysis, The serum, ELISA, Patients, Traumatic Brain Injury

Received: 16 Oct 2018; Accepted: 24 Dec 2018.

Edited by:

Dietrich E. Lorke, Florida International University, United States

Reviewed by:

Zhihui Yang, University of Florida, United States
Claus J. Scholz, Independent researcher  

Copyright: © 2018 He, Dan, Wang, Li, Fu, Zhao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Nan Zhao, Department of Neurosurgery, The First Hospital of Kunming, Kunming, China,
Prof. Ting-Hua Wang, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China,