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Differentially expressed ncRNAs derived from circulating exosomes in the pathogenesis of rat spinal cord injury

ABSTRACT: This study was originally designed to have a general overview of differentially expressed ncRNAs including miRNAs, circRNAs and lncRNAs, from circulating exosomes in SCI rats in comparison with the control rats.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE213561 | GEO | 2022/11/08

REPOSITORIES: GEO

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Umbilical Mesenchymal Stem Cell-derived Exosomes Facilitate Spinal Cord Functional Recovery Through miR-199a-3p/145-5p mediated NGF/TrkA Signaling Pathway in Rats

Project description:Background: Though exosomes, as the by-products of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal cord injury (SCI), it remains unclear through which manner exosomes act. Aim: In order to figure out whether exosomes attenuate lesion size of SCI by the amelioration of neuronal injury triggered by secondary inflammatory storm and induction of inner motivation of neurite outgrowth, we designed and performed this experiment. Methods: We determined absolute contents of all exosomal miRNAs and investigated the potential mechanisms of miR-199a-3p/145-5p in inducing neurite outgrowth in vivo and vitro. Results: miR-199a-3p/145-5p, which were relatively top-ranking miRNAs in exosomes, promoted PC12 cells differentiation suppressed by lipopolysaccharide (LPS) in vitro through the modulation of NGF/TrkA pathway. We also demonstrated that Cblb was the direct target of miR-199a-3p and Cbl was the direct target of miR-145-5p. Cblb and Cbl genes knock down revealed that TrkA ubiquitylation level significantly decreased, subsequently, activating the NGF/TrkA downstream pathways Akt and Erk. In return, overexpression of Cblb and Cbl suggested that TrkA ubiquitylation level significantly increased, subsequently, inactivating the NGF/TrkA downstream pathways Akt and Erk. Western blot and co-immunoprecipitation confirmed the direct interaction between TrkA and Cblb, TrkA and Cbl. In vivo experiment, exosomal miR-199a-3p/145-5p were found to up-regulate TrkA expression in the lesion site and promote locomotor function of SCI rats as well. Conclusion: In summary, our study suggested that hUC-MSCs derived exosomes may treat SCI by transferring miR-199a-3p/145-5p to neurons, and modulating TrkA ubiquitylation, and strengthening the NGF/TrkA signaling pathway in SCI rats.

2020-12-08 | GSE159814 | GEO

The research on transcriptional profiling in plasma exosomes of SD rats: SAH vs Sham

Project description:Transcriptional profiling of plasma exosomes came from SD rats that underwent subarachnoid hemorrhage (SAH) and sham operation (Sham) rats. The goal was to identify the changes of RNA in plasma exosomes after subarachnoid hemorrhage in SD rats.

2023-10-18 | GSE230400 | GEO

Fibroblasts orchestrate the pathogenesis of fibrotic and glial scar in spinal cord injury

Project description:Spinal cord injury (SCI) is a severe neurological dysfunction, and its pathogenesis remains inadequately understood. Here, to spatiotemporally decode the cellular and molecular pathogenesis of SCI, we performed spatial transcriptomics analysis of 12,930 single cells from 21 samples of SCI contusion model mice. We identified the specific cellular subtypes, differentially expressed genes (DEGs), cell signaling networks, site-specific genes (SSGs), and transcription factors involved in SCI. Our analysis indicated that fibroblasts served as the hub of intracellular communication in the SCI site, sent continuous immune signals to neurocytes, and induced the other cell types to express high levels of the fibroblast marker gene Col1a2. Pseudotime analysis visualized trajectories that emerged from fibroblasts, passed through microglia and ended at neurons after SCI. When the proportion of fibroblasts and their cellular communications were attenuated by solu-medrol treatment, the BMS and MEP performance of SCI mice increased significantly; moreover, the ratio of Col1a2+ cells decreased markedly, and a new subtype of fibroblasts expressing Arg1 appeared. Our results highlight the vital pathological position of fibroblasts and indicate it as a significant therapeutic target for SCI.

2022-11-27 | GSE190910 | GEO

Differentially expressed genes of C2C12 cells influenced by murine pancreatic cancer derived exosomes

Project description:Mice pancreatic cancer derived exosomes(KPC-exosomes) could induce skeletal muscle cells(C2C12) insulin resistance and exosomal microRNAs (miRNAs) may exert an important effect (Sci Rep. 2017;7(1):5384). The data set GSE95741 provided the differentially expressed micro RNAs. In this work, we aim to detect the differentially expressed genes and explore the intrinsic link.

2022-01-01 | GSE174058 | GEO

The profile of circular RNA in hypoxic exosomes from lung adenocarcinoma cell line

Project description:Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor prognosis of patients. Exosomes are involved in mediating cellular environment interactions. circRNAs are a class of non-coding RNAs (ncRNAs) broadly expressed in cells and exosomes. However, in lung adenocarcinoma tumor development, functions and regulatory mechanisms of exosomal circ-RNAs induced by hypoxia remain poorly understood.To further explore the differences in recombinant RNA expression in hypoxic and normoxic exosomes derived from lung adenocarcinoma cell line

2023-01-21 | GSE144053 | GEO

Urinary bladder post-spinal cord injury: time-points

Project description:Previously, we demonstrated using a rat model of spinal cord injury (SCI) that bladder wall tissue compliance significantly increased within the first 2 weeks following injury. In order to explore the potential molecular-level mechanisms of this event, the present study quantified molecules pertinent to bladder tissue remodeling and changes in mechanical properties. An initial gene array analysis followed by real-time qPCR revealed that the message levels for tropoelastin and lysyl oxidase were as high as 8-fold in SCI rats compared to normal. Furthermore, both the message and protein levels of TGF-beta1 and IGF-1, known stimulators of elastin synthesis, in SCI rat bladders were significantly higher compared to those of normal rats. Taken together, it can be speculated that functional changes of the bladder associated with SCI induce release of select growth factors, which, in turn, stimulate elastogenesis that lead to alteration of biomechanical properties of the wall tissue.

2008-12-25 | GSE14096 | GEO

Differential Expression profiles of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury

Project description:The goals of this study are to screen differential expression profiles of tRNA-Derived small RNAs (tsRNAs) in rats after traumatic spinal cord injury (SCI) using next-generation sequencing and qRT-PCR.As a result, in rat spinal cord 1 day after contusion, totally 297 tsRNAs differentially expressed were identified. 155 tsRNAs were significantly differentially expressed: 91 were significantly up-regulated, while 64 were significantly down-regulated after SCI (folding change>1.5; P<0.05).Next, four tsRNAs were selected to be verified by qRT-PCR. Taken together,this study explored, for the first time, the significant alteration of tsRNA expression profiles after traumatic SCI in rats and offered deep insights into many possible treatment targets of SCI by regulating tsRNAs.

2020-01-24 | GSE133157 | GEO

microRNA profiles of exosomes: Exosomes from Pooled Healthy donors' serum vs. Exosomes from Pooled NPC Patients' serum

Project description:microRNA profiles of Exosomes from Pooled NPC Patients serum comparing Control Exosomes from Healthy donors serum Two-condition experiment, Exosomes from Pooled Healthy donors serum vs. Exosomes from Pooled NPC Patients serum. Biological replicates: 1 Exosomes from Pooled Healthy donors serum, 1 Exosomes from Pooled NPC Patients serum,

2014-05-06 | E-GEOD-57319 | biostudies-arrayexpress

Circular RNAs expression profiles and potential key molecules incompletely transected spinal cord injury.

Project description:Circular RNA is implicated in numerous diseases and conditions, including traumatic injury to the central nervoussystem. However, we know little regarding their role in completely transected spinal cord injury (SCI). Our studyused high-throughput sequencing to analyze circular RNA expression in rats after experimental completetransection of spinal cord. We found differential expression in 400 circular RNAs after SCI, with 249 significantlyup-regulated and 151 significantly down-regulated. We then selected five circular RNAs for qRT-PCR validation,and the results were in agreement with RNA sequencing. Additionally, we predicted the function of circular RNAin SCI through GO and KEGG analyses, as well as the construction of circRNA/microRNA interaction networks.Furthermore, we identified circular RNA chr9:1829226-1834212 and mRNA Hdac11 as key molecules after SCI.In conclusion, this study is the first to characterize circular RNA function in rats after completely transected SCI,through identifying their differential expression. Our results provide insight into the mechanism and therapeutictargets of SCI.

2020-08-28 | GSE156999 | GEO

Effect of inhibition of oxidative stress on transcriptome profiles in rats with spinal cord injury.

Project description:The occurrence and development of secondary injury after spinal cord injury (SCI) is a key role affecting SCI recovery, and oxidative stress plays an important role in secondary injury. α-lipoic acid (ALA) is recognized as a powerful antioxidant that mitigates secondary damage and exerts neuroprotective effects. However, the mechanism by which ALA provides antioxidant role remains unknown. The application of ALA to rats after SCI was used to explore the effect of ALA on local gene transcription and expression after SCI and its role in SCI recovery.

2024-04-29 | GSE242507 | GEO

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