Effect of M2 macrophage adoptive transfer on transcriptome profile of injured spinal cords in rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC6690136 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Effect of M2 macrophage adoptive transfer on transcriptome profile of injured spinal cords in rats.
Chen Jing J Wu Yan Y Duan Fei-Xiang FX Wang Sai-Nan SN Guo Xue-Yan XY Ding Shu-Qin SQ Zhou Ji-Hong JH Hu Jian-Guo JG Lü He-Zuo HZ
Experimental biology and medicine (Maywood, N.J.) 20190603 11
Similar Datasets
Project description:Spinal cord injury (SCI) is a serious condition that results in disability and has a high morbidity rate; its treatment is very difficult. Although troxerutin and cerebroprotein hydrolysate (TCH) injections have been extensively used in clinics in China for the treatment of traumatic brain injury (TBI) and cerebral stroke, the potential efficacy of TCH injection in the treatment of SCI has never been revealed. In this study, the effects of administering TCH injections on neurological recovery in post-SCI rats were first tested with regard to the behavior and histology; subsequently, the specific expression profile of mRNAs and long noncoding RNAs (LncRNAs) in their spinal cords were conducted using RNA sequencing (RNA-seq). The LncRNA-mRNA networks were also elucidated. After SCI, we found that TCH injection with the right dose is effective for the recovery of locomotion function and repairing of the damaged tissue in the spinal cord; TCH injection is also discovered to have a role in the regulation of 443 differentially expressed genes (DEGs) and 27 differentially expressed LncRNAs (DELs) that are identified to have multiple functions, including locomotion, blood vessel morphogenesis, thiamine metabolism, Hippo signaling pathway, and axon guidance, by applying the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. In addition, it is revealed that, after SCI, the highly expressed LncRNA AABR07071383.1 in the post-SCI cis/trans-regulates the expression of mRNA Acpp mRNA that encodes a key enzyme involved in the metabolic process of thiamine in the abirritation of the dorsal root ganglion (DRG), which implies that TCH injection may be more effective when administered with benfotiamine (a common treatment drug).
| S-EPMC7424371 | biostudies-literature
Project description:BackgroundRecent studies have found that probenecid has neuroprotective and reparative effects on central nervous system injuries. However, its effect on genome-wide transcription in acute spinal cord injury (SCI) remains unknown. In the present study, RNA sequencing (RNA-Seq) is used to analyze the effect of probenecid on the local expression of gene transcription 8 h after spinal injury.MethodsAn Infinite Horizon impactor was used to perform contusive SCI in mice. The SCI model was made by using a rod (1.3 mm diameter) with a force of 50 Kdynes. Sham-operated mice only received a laminectomy without contusive injury. The injured mice were randomly assigned into either the control (SCI_C) or probenecid injection (SCI_P) group. In the latter group, the probenecid drug was intraperitoneally injected (0.5 mg/kg) immediately following injury. Eight hours after the injury or laminectomy, the spinal cords were removed from the mice in both groups. The total RNAs were extracted and purified for library preparation and transcriptome sequencing. Differential gene expressions (DEGs) of the three groups-sham, SCI_C and SCI_P-were analyzed using a DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were performed using a GOseq R package and KOBAS software. Real-time quantitative reverse-transcriptase polymerase chain reaction was used to validate RNA-Seq results.ResultsRNA-Seq showed that, compared to the SCI_C group, the number of DEGs was 641 in the SCI_P group (286 upregulated and 355 downregulated). According to GO analysis, DEGs were most enriched in extracellular matrix (ECM), collagen trimer, protein bounding and sequence specific DNA binding. KEGG analysis showed that the most enriched pathways included: cell adhesion molecules, Leukocyte transendothelial migration, ECM-receptor interactions, PI3K-Akt signaling pathways, hematopoietic cell lineages, focal adhesions, the Rap1 signaling pathway, etc. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA554464).
| S-EPMC6944129 | biostudies-literature
Project description: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).
| S-EPMC7248530 | biostudies-literature
Project description:LncRNAs played a crucial role in the cell growth, development and some diseases relating to central nerve system.This study suggest that with regulating the LncRNAs expression level we might design novel therapy for spinalcord injury. In this dataset, we profiled the expression pattern of LncRNAs by microarray method after spinal cord injury (SCI). Through Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis seek LncRNAs potential function in the repair of spinal cord injury. Fifteen samples were analyzed. In these sample, we divided into five groups (sham operation, 1 day post-injured, 3 days post-injured, 1 week post-injued and 3 weeks post-injured) and each group contained three mice.After RNA extraction,RNA form mice in the same group were mixed by equal mass for the preparation of microarray.Compared with spinal cord without injury, the differential expression level of LncRNAs had a few changes at 1day post-injury, reached the peak at 1 week after SCI, and subsequently declined until 3 weeks post-injury. Genes with an FDR≤0.05 and a fold-change ≥2 were selected. Subsequently we analysis the significant differential expression genes.
2015-09-01 | E-GEOD-67515 | biostudies-arrayexpress
Project description:LncRNAs played a crucial role in the cell growth, development and some diseases relating to central nerve system.This study suggest that with regulating the LncRNAs expression level we might design novel therapy for spinalcord injury. In this dataset, we profiled the expression pattern of LncRNAs by microarray method after spinal cord injury (SCI). Through Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis seek LncRNAs potential function in the repair of spinal cord injury.
2015-09-01 | GSE67515 | GEO
Project description:Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology.RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n?=?3 in every group). Compared with the sham-control group, the number of differentially expressed genes was 1797 in the acute phase (1223 upregulated and 574 downregulated), 6590 in the subacute phase (3460 upregulated and 3130 downregulated), and 3499 in the chronic phase (1866 upregulated and 1633 downregulated), with an adjusted P-value <0.05 by DESeq. Gene ontology (GO) enrichment analysis showed that differentially expressed genes were most enriched in immune response, MHC protein complex, antigen processing and presentation, translation-related genes, structural constituent of ribosome, ion gated channel activity, small GTPase mediated signal transduction and cytokine and/or chemokine activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most enriched pathways included ribosome, antigen processing and presentation, retrograde endocannabinoid signaling, axon guidance, dopaminergic synapses, glutamatergic synapses, GABAergic synapses, TNF, HIF-1, Toll-like receptor, NF-kappa B, NOD-like receptor, cAMP, calcium, oxytocin, Rap1, B cell receptor and chemokine signaling pathway.This study has not only characterized changes in global gene expression through various stages of SCI progression in rats, but has also systematically identified the critical genes and signaling pathways in SCI pathology. These results will expand our understanding of the complex molecular mechanisms involved in SCI and provide a foundation for future studies of spinal cord tissue damage and repair. The sequence data from this study have been deposited into Sequence Read Archive ( http://www.ncbi.nlm.nih.gov/sra ; accession number PRJNA318311).
| S-EPMC5312572 | biostudies-literature
Project description:C2D macrophage cells protect immunocompromised mice from experimentally induced pneumonias after intraperitoneal (i.p.) adoptive transfer. These macrophage cells are immature and display minimal activity in vitro. Therefore, we wanted to understand how adoptive transfer affected these cells. We believe that the in vivo environment affects the phenotypic and functional characteristics of macrophages that help maintain the physiological integrity of the host. To test this hypothesis, we characterized the trafficking patterns and cellular changes of the established macrophage C2D cell line after adoptive transfer. We examined phenotypic changes of the C2D macrophage cells in vivo with and without stimulation with gamma interferon (IFN-gamma). After in vivo i.p. adoptive transfer, C2D macrophage cells trafficked to the lungs, spleen, lymph nodes, and bone marrow of recipient mice. The cells were detected for as long as 2 months, and the cells expressed increased levels of CD11b, c-fms, and F4/80 on their surface, becoming more differentiated macrophages compared to cells maintained in vitro. Upon in vivo stimulation with IFN-gamma, c-fms levels decreased while Gr-1 levels increased compared to in vivo, unstimulated, phosphate-buffered saline-injected controls. These responses were independent of the genetic backgrounds of the recipient mice. These data support the hypothesis and indicate that C2D macrophage cells respond to in vivo signals that are absent during in vitro culture.
| S-EPMC2238063 | biostudies-literature
Project description:This laboratory works on selectins and their carbohydrate ligands in lymphocyte homing and inflammation. The lab also studies heparin-degrading endosulfatases and their roles in regulating the interactions of growth factors and morphogens with proteoglycans. The purpose of the experiment is to examine gene expression profiles in spinal cords of injured as a function of time after a contusion injury. The tissue will be generated in the lab of Linda Noble, Professor in the Department of Neurological Surgery at UCSF who is an expert on the pathogenesis of spinal cord injury. Wild-type male C57B/6 mice (8-10 weeks of age) were used. Injuries were produced by contusion. Spinal cords from control mice (uninjured) and experimental (injured) mice were processed (4 and 7 days after injury). A 3 mm length of spinal cord (centered at the injury) and a 3 mm segment from a distant site were isolated from each animal. Tissue from 3 mice were pooled for each sample. Three replicate samples per treatment group were processed for RNA. Thus, a total of 18 RNA samples were hybridized to 18 gene chips. The analysis will determine whether specific glycosylation changes accompany spinal cord injury. Of particular interest are changes in the sulfation profile of proteoglycan GAG chains (e.g., chondroitin sulfate) and in the appearance of potential carbohydrate ligands for infiltrating leukocytes bearing L-selectin or other endogenous lectins.
2011-02-17 | E-GEOD-27359 | biostudies-arrayexpress
Project description:This laboratory works on selectins and their carbohydrate ligands in lymphocyte homing and inflammation. The lab also studies heparin-degrading endosulfatases and their roles in regulating the interactions of growth factors and morphogens with proteoglycans.
2011-02-17 | GSE27359 | GEO
Project description:Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments.
| S-EPMC6293371 | biostudies-literature