Gene expression profiles reveal key pathways and genes associated with neuropathic pain in patients with spinal cord injury

Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced concurrently. Pain after SCI may be refractory to treatments and negatively affects quality of life. Previously, we analyzed whole blood gene expression in individuals with chronic SCI compared to able-bodied (AB) individuals. Most participants with SCI reported pain (N = 19/28). Here, we examined gene expression of participants with SCI by pain status. Compared to AB, participants with SCI with pain had 468 differentially expressed (DE) genes; participants without pain had 564 DE genes (FDR < 0.05). Among DE genes distinct to participants with SCI with pain, Gene Ontology Biological Process (GOBP) analysis showed upregulated genes were enriched in categories related to T cell activation or inflammation; downregulated genes were enriched in categories related to protein proteolysis and catabolism. Although most participants with pain reported multiple pain types concurrently, we performed a preliminary comparison of gene expression by worst pain problem type. Compared to AB, participants with SCI who ranked neuropathic (N = 9) as worst had one distinct DE gene (TMEM156); participants who ranked nociceptive (N = 10) as worst had 61 distinct DE genes (FDR < 0.05). In the nociceptive group, the GOBP category with the lowest P-value identified among upregulated genes was “positive regulation of T cell activation”; among downregulated genes it was “receptor tyrosine kinase binding”. An exploratory comparison of pain groups by principal components analysis also showed that the nociceptive group was enriched in T-cell related genes. A correlation analysis identified genes significantly correlated with pain intensity in the neuropathic or nociceptive groups (N = 145, 65, respectively, Pearson’s correlation r > 0.8). While this pilot study highlights challenges of identifying gene expression profiles that correlate with specific types of pain in individuals with SCI, it suggests that T-cell signaling should be further investigated in this context.

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Identification Of Exosomal LncRNAs From Peripheral Blood In Spinal Cord Injury Mouse Model

10.21203/rs.3.rs-430002/v1 ◽

2021 ◽

Author(s):

Jian-an Li ◽

Ming-peng Shi ◽

Lin Cong ◽

Ming-yu Gu ◽

Yi-heng Chen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Peripheral Blood ◽

Regulatory Networks ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Repair Process ◽

Neurological Dysfunction ◽

Cord Injury ◽

Non Coding Rnas

Abstract Background Spinal Cord Injury ( SCI ) is a disease leading to permanent neurological dysfunction. In recent years, exosomes and non-coding RNAs have been considered as potential therapeutic agents for spinal cord injury. Based on ceRNA regulatory network, the role of non-coding RNAs has been paid attention to, and some genes related to the pathological process after spinal cord injury have been found. However, most gene studies only focus on exosomes and non-coding RNAs in spinal cord injury sites, and few genes related to spinal cord injury repair have been found. Objective We aimed to identify exosomes and non-coding RNA in peripheral blood after spinal cord injury, and to predict its role in spinal cord injury according to gene expression profiles. Materials and methods After successful modeling of spinal cord injury, rat exosomes were extracted from peripheral blood.Western-Blot was used to identify exosomes. After RNA was extracted from exosomes, total transcriptome sequencing and differential gene GO and KEGG Pathway analysis were performed. We selected potential genes for quantitative Real-Time PCR (qRT-PCR) assays and predicted their potential regulatory networks. Results The successful establishment of spinal cord injury model was confirmed by Tarlov’s scores, and the extracted exosomes were confirmed by Western-Blot and electron microscopy. Among the significantly differentially expressed lncRNAs, XR_351404, XR_353833, XR_590719, XR_590076, and XR_591455 were associated with miRNA related to repair after spinal cord injury. Conclusions The regulatory effect of this network may play a key role in the repair process of SCI. The differential lncRNAs we found may serve as therapeutic targets and diagnostic biomarkers for SCI.

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Screening Circular RNA Related to Vascular Endothelial Proliferation, Migration and Angiogenesis in Spinal Cord Injury by RNA Sequencing

10.21203/rs.3.rs-127498/v1 ◽

2020 ◽

Author(s):

Xin Ye ◽

Yilei Chen ◽

Jiasheng Wang ◽

Jian Chen ◽

Ying Yao ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Early Stage ◽

Expression Profiles ◽

Expression Patterns ◽

Circular Rnas ◽

Vascular Endothelial ◽

Endothelial Proliferation ◽

Cord Injury

Abstract Background: Traumatic spinal cord injury (SCI) causes high rates of worldwide morbidity because of the complex secondary injury. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs, which have recently been recognized as important regulators of gene expression and pathological processes. In this study, we have attempted to elucidate the expression profiles of circRNAs in a mouse model of SCI and comprehensively understand vascular endothelial proliferation, migration and angiogenesis in the early stage of secondary injury.Methods: Deep RNA sequencing (RNA-seq) and bioinformatic analysis including GO enrichment analysis, KEGG pathway analysis and circRNA-miRNA-mRNA network construction were performed to investigate the expression patterns of circRNAs in mouse spinal cord after SCI (n= 3 per group) for three days and explore the differentially expressed circRNAs related to vascular endothelial proliferation, migration and angiogenesis. Results: Total of 1288 circRNAs were altered (>2-fold change, p<0.05) in the spinal cord after SCI, including 991 were upregulated and 297 were downregulated. Meanwhile we constructed a circRNA-mRNA network to predict their functions for circRNAs can act as “miRNA sponges”,. We next analyzed the altered circRNAs related to vascular endothelial proliferation, migration and angiogenesis by GO and KEGG analyses. 121 circRNAs were found to correlating to vascular endothelial proliferation，migration and angiogenesis in spinal cord after SCI. Conclusions: Our results reveal that circRNAs locally regulate their related protein-gene expression and play key roles in the vascular endothelial proliferation, migration and angiogenesis of SCI.

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Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury

Physiological Genomics ◽

10.1152/physiolgenomics.00064.2019 ◽

2020 ◽

Vol 52 (2) ◽

pp. 71-80

Author(s):

Michael A. Petrie ◽

Arpit Sharma ◽

Eric B. Taylor ◽

Manish Suneja ◽

Richard K. Shields

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Specific Gene ◽

Muscle Exercise ◽

Gene Sets ◽

Cord Injury ◽

Key Pathways

Exercise attenuates the development of chronic noncommunicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short- or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed by a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for metabolism (38 gene sets), cell cycle (36 gene sets), disease (27 gene sets), gene expression and transcription (22 gene sets), organelle biogenesis (4 gene sets), cellular response to stimuli (8 gene sets), immune system (8 gene sets), vesicle-mediated transport (4 gene sets), and transport of small molecules (3 gene sets). Specific gene expression included: oxidative catabolism of glucose including PDHB ( P < 0.001), PDHX ( P < 0.001), MPC1 ( P < 0.009), and MPC2 ( P < 0.007); Oxidative phosphorylation genes including SDHA ( P < 0.006), SDHB ( P < 0.001), NDUFB1 ( P < 0.002), NDUFA2 ( P < 0.001); transcription genes including PGC1α ( P < 0.030) and PRKAB2 ( P < 0.011); hypertrophy gene MSTN ( P < 0.001); and the myokine generating FNDC5 gene ( P < 0.008). Long-term electrically induced exercise demethylated the major transcription factor PGC1a. Taken together, these findings support that long-term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.

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