TMT-based proteomics analysis to screen potential biomarkers of acute-phase TBI in rats

Abstract

Aims: Traumatic brain injury (TBI) is a common nervous system injury. However, the detailed mechanisms about functional dysregulation and dignostic biomarkers post-TBI are still unclear. So we aimed to identify potential differentially expressed proteins and genes in TBI for clinical diagnosis and therapeutic purposes.

Main methods: Rat TBI model was established by the weight-drop method. First, through TMT-proteomics, we screened for the change in the proteins expression profile acute phase post-TBI. The DAVID and Reactome databases were used to analyze and visualize the dysregulation proteins. Then, using publicly available microarray datasets GSE45997, differentially expressed genes (DGEs) were identified for the 24 h post-TBI stage. Also, the proteomic data were compared with microarray data to analyze the similarity.

Key findings: We found significant proteomics and transcriptomic changes in post-TBI samples. 989, 881, 832, 1057 proteins were quantitated at 1 h, 6 h, 24 h, and 3 d post-injury correspondingly. Concerning proteomics findings, oxygen transport, acute-phase response, and negative regulation of endopeptidase activity were influenced throughout the acute phrase of TBI. Also, pathways related to scavenging of heme from plasma, binding, and uptake of ligands by scavenger receptors were highly enriched in all time-points of TBI samples.

Significance: We noticed that the interaction-networks trend to get complicated with more node connections following the progression of TBI. We inferred that Hk-1, PRKAR2A, and MBP could be novel candidate biomarkers related to time-injury in acute-phase TBI. Also, Ceruloplasmin and Complement C3 were found to be important proteins and genes are involved in the TBI.

Keywords: Biomarkers; Protein-protein interaction networks; Quantitative proteomics; TMT; Traumatic brain injury.