A Selective P2Y Purinergic Receptor Agonist 2-MesADP Enhances Locomotor Recovery after Acute Spinal Cord Injury

2020 ◽  
Vol 83 (2) ◽  
pp. 195-212
Author(s):  
Ziru Zhao ◽  
Xiao Hu ◽  
Zhourui Wu ◽  
Qi Chen ◽  
Qihui Shao
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Apoptosis ◽  
Purinergic Receptor ◽  
Expression Patterns ◽  
Gene Profiling ◽  
Locomotor Recovery ◽  
Wnt Signal Pathway ◽  
Cord Injury

Introduction: Spinal cord injury (SCI) causes most severe motor and sensory dysfunctions. In Chinese traditional medicine, the agonist of a purinergic receptor is believed to have a positive effect on SCIs, and 2-Methylthio-adenosine-5′-diphosphate (2-MesADP) is a selective agonist of the P2Y purinergic receptor. Methods: To investigate its therapeutic function and molecular mechanism in SCI, transcriptome analysis associated with weighted gene co-expression network analysis (WGCNA) was carried out at various time points after T9 crush injury. Results: 2-MesADP demonstrated recovery of limb motor function at the 6 weeks after injury, accompanied by neuronal regeneration and axon remyelination at 2 and 6 weeks. Furthermore, gene profiling revealed alternated gene expression with the treatment of 2-MesADP. These genes were assigned to a total of 38 modules, followed by gene ontology analysis; of these, 18 represented neuronal apoptosis and regeneration, immune response, synaptic transmission, cell cycle, and angiogenesis. In the neuronal apoptosis and regeneration module, Nefh, NeuroD6, and Dcx in the 2-MesADP group were noticed due to their interesting expression pattern. The gene expression patterns of Mag, Mog, and Cnp, which played key roles in myelination, were significantly changed with the treatment of 2-MesADP. Wnt signal pathway was the most important pathway in 2-MesADP treatment for acute SCI. Conclusion: 2-MesADP enhanced locomotor recovery in mouse SCI by altering the expression of neuronal apoptosis and remyelination-related genes and Wnt signaling pathways.

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

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.

scholarly journals PD-L1 Improves Motor Function and Alleviates Neuropathic Pain in Male Mice After Spinal Cord Injury by Inhibiting MAPK Pathway

2021 ◽  
Author(s):  
Jiangang Shi ◽  
FanQi Kong ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
FuDong Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Inflammatory Response ◽  
Mapk Pathway ◽  
Expression Patterns ◽  
Motor Dysfunction ◽  
Locomotor Recovery ◽  
Cord Injury

Abstract Background Traumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep) that remains uncured yet. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment, and the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of research has begun to investigate the effect of PD-L1 on macrophages and microglia. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we tested the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through macrophages and microglia. Methods The mice SCI model was employed to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI. Results In present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia. PD-L1 knockout (KO) mice showed poor locomotor recovery and serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2. Conclusions Our observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for prevention and treatment of this traumatic condition.

scholarly journals PD-L1 Improves Motor Function and Alleviates Neuropathic Pain in Male Mice After Spinal Cord Injury by Inhibiting MAPK Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Fanqi Kong ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
Fudong Li ◽  
Feng Lin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Inflammatory Response ◽  
Mapk Pathway ◽  
Expression Patterns ◽  
Motor Dysfunction ◽  
Locomotor Recovery ◽  
Cord Injury

BackgroundTraumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep), which has not yet been effectively cured. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment. However, the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of researches have begun to investigate the effect of PD-L1 on macrophages and microglia in recent years. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we proposed the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through regulating macrophages and microglia.MethodsThe mice SCI model was established to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI.ResultsIn present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia at the injury epicenter. PD-L1 knockout (KO) mice showed worse locomotor recovery and more serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2.ConclusionsOur observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for the prevention and treatment of this traumatic condition.

233-LB: Spinal Cord Injury Inhibited-FGF21 Signaling Is Associated with Dysregulation of Metabolic Gene Expression in Mouse Liver and Adipose Tissue

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 233-LB
Author(s):  
XIN-HUA LIU ◽  
LAUREN HARLOW ◽  
ZACHARY GRAHAM ◽  
JOSHUA F. YARROW ◽  
KENNETH CUSI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Mouse Liver ◽  
Metabolic Gene ◽  
Metabolic Gene Expression ◽  
Cord Injury
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