scholarly journals Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature

2019 ◽  
Author(s):  
Shuang Qi ◽  
Zinan Li ◽  
Shanshan Yu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Regulatory Network ◽  
Metabolic Process ◽  
Differentially Expressed ◽  
Transcription Profile ◽  
Comparative Toxicogenomics Database ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Cluster 2

Abstract Background: To gain a better understanding of the molecular mechanisms of spinal cord injury and the effects of Neurotrophin-3, differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods: The miRNA transcription profile of GSE82195 and the mRNA transcription profile of GSE82196 including dorsal root ganglion (DRG) tissue samples of normal adult rat (none, n=6), 10 weeks post-pyramidotomy, intramuscular AAV-1 GFP (injury, n=6) and 10 weeks post-pyramidotomy, intramuscular AAV-1 prepro-neurotrophin-3 (NT-3, n=6) were downloaded from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/). Then, differentially expressed RNAs (DERs) including DEmiRNAs and DEGs were identified using limma. The noise-robust soft clustering of the intersection DERs was performed using Mfuzz package. Additionally, the integrated miRNAs–targets regulatory network was constructed using Cytoscape. Finally, the Comparative Toxicogenomics Database 2019 update (http://ctd.mdibl.org/) were used to search the central nervous system injury related pathway. Results: A total of 444 DERs including 382 DEGs and 62 DEmiRNAs were screened between group injury and group none whlie 576 DERs including 523 DEGs and 55 DEmiRNAs were screened between group NT-3 and group injury. Moreover, 80 intersections DERs were identified.Two clusters were obtained including cluster 1 (including rno-miR-3072, rno-miR-667-5p and so on) and cluster 2 (OPRL1, GHSR and so on). DREs in cluster 1 were firstly significantly downregulated in group injury and subsequently were significantly upregulated in group NT-3. DERs in cluster 2 were firstly upregulated in group injury and subsequently downregulated in group NT-3. OPRL1 and GHSR were enriched in the KEGG pathway of Neuroactive ligand-receptor interaction which is also found in the Comparative Toxicogenomics Database 2019 update. OPRL1 was involved in the chemical homeostasis and ion homeostasis while GHSR was related to the regulation of fatty acid metabolic process and regulation of cellular ketone metabolic process. Conclusion: DEmiRNAs rno-miR-3072 and rno-miR-667-5p and DEGs OPRL1 and GHSR might participate in the pathogenesis of neurological injury and the neurotrophin-3 treatment. Keywords: spinal cord injury, differentially expressed miRNA, differentially expressed gene, regulatory network, Neurotrophin-3

scholarly journals Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature

2020 ◽  
Author(s):  
Shuang Qi ◽  
Zinan Li ◽  
Shanshan Yu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Ion Homeostasis ◽  
Metabolic Process ◽  
Neurological Injury ◽  
Receptor Interaction ◽  
Transcription Profile ◽  
Neurotrophin 3 ◽  
Cord Injury

Abstract Background To gain a better understanding of the molecular mechanisms of spinal cord injury and the effects of Neurotrophin-3, differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods The miRNA transcription profile of GSE82195 and the mRNA transcription profile of GSE82196 were downloaded from the Gene Expression Omnibus (GEO). Then, DERs were identified using limma. The noise-robust soft clustering of the intersection DERs was performed using Mfuzz package. Additionally, the integrated miRNAs–targets regulatory network was constructed using Cytoscape. Finally, the Comparative Toxicogenomics Database 2019 update was used to search the central nervous system injury related pathway. Results A total of 444 DERs including 382 DEGs and 62 DEmiRNAs were screened between group injury and group none whlie 576 DERs including 523 DEGs and 55 DEmiRNAs were screened between group NT-3 and group injury. Moreover, 80 intersections DERs were identified. DREs in cluster 1 were firstly significantly down-regulated in group injury and subsequently were significantly up-regulated in group NT-3. DERs in cluster 2 were firstly up-regulated in group injury and subsequently down-regulated in group NT-3. OPRL1 and GHSR were enriched in the KEGG pathway of Neuroactive ligand-receptor interaction. OPRL1 was involved in the chemical homeostasis and ion homeostasis while GHSR was related to the regulation of fatty acid metabolic process and regulation of cellular ketone metabolic process. Conclusion rno-miR-3072 and rno-miR-667-5p and OPRL1 and GHSR might participate in the pathogenesis of neurological injury and the neurotrophin-3 treatment.

scholarly journals Identification of Key eRNAs for Spinal Cord Injury by Integrated Multinomial Bioinformatics Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Runzhi Huang ◽  
Siqiao Wang ◽  
Rui Zhu ◽  
Shuyuan Xian ◽  
Zongqiang Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Microarray Data ◽  
Immune Cells ◽  
Regulatory Network ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Cord Injury

Background: Spinal cord injury (SCI) is a severe neurological deficit affecting both young and older people worldwide. The potential role of key enhancer RNAs (eRNAs) in SCI remains elusive, which is a prominent challenge in the trauma repair process. This study aims to investigate the roles of key eRNAs, transcription factors (TFs), signaling pathways, and small-molecule inhibitors in SCI using multi-omics bioinformatics analysis.Methods: Microarray data of peripheral blood mononuclear cell (PBMC) samples from 27 healthy volunteers and 25 chronic-phase SCI patients were retrieved from the Gene Expression Omnibus database. Differentially expressed transcription factors (DETFs), differentially expressed enhancer RNAs (DEeRNAs), and differentially expressed target genes (DETGs) were identified using the Linear Models for Microarray Data (limma) package. Fraction of immune cells was estimated using CIBERSORT algorithm. Gene Set Variation Analysis (GSVA) was applied to identify the downstream signaling pathways. The eRNA regulatory network was constructed based on the correlation results. Connectivity Map (CMap) database was used to find potential drugs for SCI patients. The cellular communication analysis was performed to explore the molecular regulation mechanism of SCI based on single-cell RNA sequencing (scRNA-seq) data. Chromatin immunoprecipitation sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data were used to validate the key regulatory mechanisms. scRNA-seq dataset was used to validate the cell subtype localization of the key eRNAs.Results: In total, 21 DETFs, 24 DEeRNAs, and 829 DETGs were identified. A regulatory network of 13 DETFs, six DEeRNAs, seven DETGs, two hallmark pathways, two immune cells, and six immune pathways was constructed. The link of Splicing factor proline and glutamine rich (SFPQ) (TF) and vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) (eRNA) (R = 0.990, p < 0.001, positive), VOPP1 (eRNA) and epidermal growth factor receptor (EGFR) (target gene) (R = 0.974, p < 0.001, positive), VOPP1, and T helper (Th) cells (R = −0.987, p < 0.001, negative), and VOPP1 and hallmark coagulation (R = 0.937, p < 0.001, positive) was selected. Trichostatin A was considered the best compound target to SCI-related eRNAs (specificity = 0.471, p < 0.001).Conclusion: VOPP1, upregulated by SFPQ, strengthened the transient expression of EGFR. Th cells and coagulation were the potential downstream pathways of VOPP1. This regulatory network and potential inhibitors provide novel diagnostic biomarkers and therapeutic targets for SCI.

scholarly journals Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qi Han ◽  
Josue D. Ordaz ◽  
Nai-Kui Liu ◽  
Zoe Richardson ◽  
Wei Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Enhanced Recovery ◽  
Neural Pathways ◽  
Locomotor Recovery ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Dendritic Atrophy ◽  
Descending Projections

AbstractLocomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.

Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury

2016 ◽  
Vol 94 (7) ◽  
pp. 645-652 ◽  
Author(s):  
Amgad Hanna ◽  
Daniel L. Thompson ◽  
Daniel J. Hellenbrand ◽  
Jae-Sung Lee ◽  
Casey J. Madura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Calcium Phosphate ◽  
Sustained Release ◽  
Axonal Regeneration ◽  
Neurotrophin 3 ◽  
Cord Injury

scholarly journals Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

2015 ◽  
Vol 112 (43) ◽  
pp. 13360-13365 ◽  
Author(s):  
Hongmei Duan ◽  
Weihong Ge ◽  
Aifeng Zhang ◽  
Yue Xi ◽  
Zhihua Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Cns Injury ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Transcriptome Analyses ◽  
Regeneration Capability

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.

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