The Time Sequence of Gene Expression Changes after Spinal Cord Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Surgical Procedures and Tissue Preparation
2.3. Histology
2.4. Locomotor Assessment
2.5. RNA Sample Preparation
2.6. RNA Sequencing Library Construction
2.7. Data Analysis
2.7.1. Quality Control
2.7.2. Read Mapping and Differentially Expressed Genes (DEG) Analysis
2.7.3. Statistical Analysis and Visualization of Data
2.7.4. Integrative Function Classification Analysis for DEGs
2.7.5. Time-Series DPGP Clustering Analysis
2.7.6. Gene–Drug Network Analysis
3. Results
3.1. Histological and Functional Results of SCI Models at Five Time Points
3.2. Transcriptome Sequencing Analysis
3.3. Transcriptional Waves According to the Time after SCI
3.3.1. Identification of DEGs in Each Period and Their Functional Prediction
3.3.2. Systematic DEG Classification Using the DPGP Clustering Method for Time Series Analysis
3.4. Molecular Changes Caused by SCI
3.5. Exploration of the Molecular Biological Cascade through Integrated Analysis of the Continuous Period after SCI
3.5.1. Interleukin Signaling
3.5.2. Neutrophil Degranulation, Eukaryotic Translation, and Collagen Degradation
3.5.3. LGI–ADAM Interactions, GABA Receptor, and L1CAM–Ankyrin Interactions
3.6. Gene–Drug Network Analysis Provides Potential Drug or Chemical Candidates for the Treatment of SCI
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mechanism of Action (MOA) | DEGs | Launched Drugs | Description | Genes List | Effective Period |
---|---|---|---|---|---|
Antagonist | Upregulated | Dextromethorphan | noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist | C2, C6, CYBA, CYBB, NCF1, NCF2, NCF4, RAC2, RIN3 | 1 d–3 m |
Procaine | HMGCR inhibitor, sodium channel blocker | CNN2, KCNMB4, C6, KCNN4, RIN3, CNN3 | 1 d–3 m | ||
Amiloride | sodium channel blocker | PLAU, C2, TRPV2, C7 | 1 d–1 m | ||
Dasatinib | Bcr-Abl kinase inhibitor, ephrin inhibitor, KIT inhibitor, PDGFR tyrosine kinase receptor inhibitor, SRC inhibitor, tyrosine kinase inhibitor | EPHA2, HCK, LYN, PDGFRB, FGR | 1 h–3 m | ||
Boceprevir | HCV inhibitor | CTSA, CTSK, CTSL, CTSS | 1 m–3 m | ||
Bosutinib | Abl kinase inhibitor, Bcr-Abl kinase inhibitor, SRC inhibitor | HCK, LYN, STK10, TK1 | 1 d–1w | ||
Agonist | Downregulated | L-glutamic acid | glutamate receptor agonist | FOLH1, GLS2, GRIN2C, GRM1, GRM3, GRM4, SLC1A2, SLC25A18, BCAT1, GAD1, GOT1, GRIA2, GRIA4, GRIN1, GRM8, SYN1, ABAT, GAD2, GRIA3, GRIN2A | 1 d–3 m |
Dehydroepiandrosterone (DHEA) | protein synthesis stimulant | GABRA2, GABRA5, GABRB2, GRIN2C, GABRA1, GABRG2, GRIN1, GABRA3, GABRB3, GABRQ, GRIN2A | 1 d–3 m | ||
(R)-(-)-apomorphine | dopamine receptor agonist | ADRA2C, HTR2C, CALY, HTR1B, HTR5A | 1 d–3 m | ||
D-serine | glutamate receptor agonist | GLRA1, GRIN2C, GRIN1, GLRA1, GRIN2A | 1 d–3 m | ||
Valproic acid | benzodiazepine receptor agonist, HDAC inhibitor | SCN1A, SCN4B, SCN8A, ABAT | 1 d, 1 m–3 m |
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Mun, S.; Han, K.; Hyun, J.K. The Time Sequence of Gene Expression Changes after Spinal Cord Injury. Cells 2022, 11, 2236. https://doi.org/10.3390/cells11142236
Mun S, Han K, Hyun JK. The Time Sequence of Gene Expression Changes after Spinal Cord Injury. Cells. 2022; 11(14):2236. https://doi.org/10.3390/cells11142236
Chicago/Turabian StyleMun, Seyoung, Kyudong Han, and Jung Keun Hyun. 2022. "The Time Sequence of Gene Expression Changes after Spinal Cord Injury" Cells 11, no. 14: 2236. https://doi.org/10.3390/cells11142236