Effect of VX‑765 on the transcriptome profile of mice spinal cords with acute injury

Chen,Jing; Chen,Jing; Chen,Jing; Chen,Jing; Chen,Jing; Chen,Yu‑Qing; Chen,Yu‑Qing; Chen,Yu‑Qing; Chen,Yu‑Qing; Chen,Yu‑Qing; Wang,Sai‑Nan; Wang,Sai‑Nan; Wang,Sai‑Nan; Wang,Sai‑Nan; Wang,Sai‑Nan; Duan,Fei‑Xiang; Duan,Fei‑Xiang; Duan,Fei‑Xiang; Duan,Fei‑Xiang; Duan,Fei‑Xiang; Shi,Yu‑Jiao; Shi,Yu‑Jiao; Shi,Yu‑Jiao; Shi,Yu‑Jiao; Shi,Yu‑Jiao; Ding,Shu‑Qin; Ding,Shu‑Qin; Ding,Shu‑Qin; Ding,Shu‑Qin; Ding,Shu‑Qin; Hu,Jian‑Guo; Hu,Jian‑Guo; Hu,Jian‑Guo; Hu,Jian‑Guo; Hu,Jian‑Guo; Lü,He‑Zuo; Lü,He‑Zuo; Lü,He‑Zuo; Lü,He‑Zuo; Lü,He‑Zuo

doi:10.3892/mmr.2020.11129

Effect of VX‑765 on the transcriptome profile of mice spinal cords with acute injury

Authors:
- Jing Chen
- Yu‑Qing Chen
- Sai‑Nan Wang
- Fei‑Xiang Duan
- Yu‑Jiao Shi
- Shu‑Qin Ding
- Jian‑Guo Hu
- He‑Zuo Lü
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Affiliations: Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
Published online on: May 5, 2020 https://doi.org/10.3892/mmr.2020.11129
Pages: 33-42
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have shown that caspase-1 plays an important role in the acute inflammatory response of spinal cord injury (SCI). VX‑765, a novel and irreversible caspase‑1 inhibitor, has been reported to effectively intervene in inflammation. However, the effect of VX‑765 on genome‑wide transcription in acutely injured spinal cords remains unknown. Therefore, in the present study, RNA‑sequencing (RNA‑Seq) was used to analyze the effect of VX‑765 on the local expression of gene transcription 8 h following injury. The differentially expressed genes (DEGs) underwent enrichment analysis of functions and pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Parallel analysis of western blot confirmed that VX‑765 can effectively inhibit the expression and activation of caspase‑1. RNA‑Seq showed that VX‑765 treatment resulted in 1,137 upregulated and 1,762 downregulated DEGs. These downregulated DEGs and their associated signaling pathways, such as focal adhesion, cytokine‑cytokine receptor interaction, leukocyte transendothelial migration, extracellular matrix‑receptor interaction, phosphatidylinositol 3‑kinase‑protein kinase B, Rap1 and hypoxia inducible factor‑1 signaling pathway, are mainly associated with inflammatory response, local hypoxia, macrophage differentiation, adhesion migration and apoptosis of local cells. This suggests that the application of VX‑765 in the acute phase can improve the local microenvironment of SCI by inhibiting caspase‑1. However, whether VX‑765 can be used as a therapeutic drug for SCI requires further exploration. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA548970).

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