Author:
Zhao Jianwei,Xu Chen,Cao Heli,Zhang Lin,Wang Xuyang,Chen Shiwen
Abstract
Background
Traumatic brain injury (TBI) is a common neurological emergency observed in hospitals. A considerable number of patients suffer from long-term disabilities after TBI. This study aimed to identify altered gene expression signatures and mechanisms related to TBI-induced chronic neuroinflammation and neurodegeneration.
Methods
An integrated analysis was performed using published RNA-sequencing studies to determine TBI-induced differentially expressed genes (DEGs). Based on the DEG data, functional annotation, signal-net, and transcription factor analyses were conducted to understand the mechanism of chronic neuroinflammation and neurodegeneration induced after TBI.
Results
Two datasets were obtained using the Gene Expression Omnibus database, of which, 6,513 DEGs were identified (6,464 upregulated and 49 downregulated). Positive regulation of biological process, positive regulation of cellular process, nucleus, and heterocyclic compound binding were Gene Ontology terms significantly enriched in post-TBI rat models. Leukocyte transendothelial migration, chemokine signaling pathway, neurotrophin signaling pathway, and longevity-regulating pathway were significantly enriched after TBI. With regard to the signal-net analysis, FOXO3, DGKZ and ILK were considered the most critical genes derived using high–betweenness centrality calculation. A total of 44 TFs, including FOXO1, SRY and KLF4, were predicted to play an important role in the upregulation of gene expression. Using integrated bioinformatics analysis, TBI was found to be associated with a significant inflammatory response and neurodegeneration. FOXO3, apolipoprotein (APOE), microtubule-associated protein tau (MAPT), and TREM2 were probably associated with the TBI pathological process. The mitochondrial electron transport chain may be associated with neurodegeneration in patients with TBI, serving as a potential therapeutic target.
Funder
Shanghai Science and Technology Commission
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
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