Research Paper Volume 16, Issue 11 pp 9990—10003

Analysis and experimental validation of genes and their transcription factor prediction in contused rat spinal cord at the intermediate phase

Zhongju Shi1, *, , Tuo Fang1, *, , Baoyou Fan1, *, , Jun Ma1, , Jianhao Wang1, , Shiqing Feng1,2, ,

  • 1 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, P.R. China
  • 2 International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, P.R. China
* Equal contribution

Received: October 23, 2023       Accepted: April 16, 2024       Published: June 2024      

https://doi.org/10.18632/aging.205912
How to Cite

Copyright: © 2024 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The intermediate phase of spinal cord injury (SCI) serves as an important target site for therapeutic mediation of SCI. However, there is a lack of insight into the mechanism of the intermediate phase of SCI. The present study aimed to investigate the molecular mechanism and the feasible treatment targets in the intermediate phase of SCI. We downloaded GSE2599 from GEO and identified 416 significant differentially expressed genes (DEGs), including 206 downregulated and 210 upregulated DEGs. Further enrichment analysis of DEGs revealed that many important biological processes and signal pathways were triggered in the injured spinal cord. Furthermore, a protein-protein interaction (PPI) network was constructed and the top 10 high-degree hub nodes were identified. Furthermore, 27 predicted transcription factors (TFs) and 136 predicted motifs were identified. We then selected insulin-like growth factor 1 (IGF1) and its predicted transcription factor, transcription factor A, mitochondrial (TFAM) for further investigation. We speculated and preliminarily confirmed that TFAM may regulate gene transcription of IGF1 and effected alterations in the function recovery of rats after SCI. These findings together provide novel information that may improve our understanding of the pathophysiological processes during the intermediate phase of SCI.

Abbreviations

SCI: spinal cord injury; DEGs: differentially expressed genes; PPI: protein-protein interaction; TFs: transcription factors; IGF1: insulin-like growth factor 1; TFAM: transcription factor A, mitochondrial; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DAVID: Database for Annotation, Visualization and Integrated Discovery; STRING: Search Tool for the Retrieval of Interacting Genes; BBB: Basso, Beattie and Bresnahan; BP: biological processes; MF: molecular function; CC: cell components; FOS: FBJ osteosarcoma oncogene; TIMP1: TIMP metallopeptidase inhibitor 1; CCL2: C-C motif chemokine ligand 2; VIM: vimentin; CALB2: calbindin 2; APOE: apolipoprotein E; PTPRC: protein tyrosine phosphatase, receptor type, C; IFNG: interferon gamma; TGFB1: transforming growth factor, beta 1; mtDNA: mitochondrial DNA.