Expression profiling of contralateral dorsal root ganglia of a rat model of complex regional pain syndrome type-I uncovers potential mechanisms involved in mirror-image pain
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ABSTRACT:
PROVIDER: PRJNA729242 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14506651.fastq.gz | Fastqsanger.gz | |||
| SRR14506652.fastq.gz | Fastqsanger.gz | |||
| SRR14506653.fastq.gz | Fastqsanger.gz | |||
| SRR14506654.fastq.gz | Fastqsanger.gz | |||
| SRR14506655.fastq.gz | Fastqsanger.gz |
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Project description:Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, including complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remained largely unknown. The purpose of this study is to perform an expression profiling to identify genes related with MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining and animal behavioral assays were used to screen potential genes in contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs. control rats. The expression changes of several representative DEGs were verified by qPCR. Bioinformatics analysis indicated that immune system process, innate immune response and cell adhesion were among the mostly enriched biological processes, which are all important processes involved in pain sensitization, neuroinflammation and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and pain mechanism in MIP. Conclusions: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for investigating MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.
2021-09-15 | GSE174299 | GEO
Project description:The development of mirror-image biology systems and related applications is hindered by the lack of effective methods to sequence mirror-image (D-) proteins. Although natural-chirality (L-) proteins can be sequenced by bottom–up liquid chromatography–tandem mass spectrometry (LC–MS/MS), the sequencing of long D-peptides and D-proteins with the same strategy requires digestion by a site-specific D-protease before mass analysis. Here we apply solid-phase peptide synthesis and native chemical ligation to chemically synthesize a mirror-image version of trypsin, a widely used protease for site-specific protein digestion. Using mirror-image trypsin digestion and LC–MS/MS, we sequence a mirror-image large subunit ribosomal protein (L25) and a mirror-image Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), and distinguish between different mutants of D-Dpo4. We also perform writing and reading of digital information in a long D-peptide of 50 amino acids. Thus, mirror-image trypsin digestion in conjunction with LC–MS/MS may facilitate practical applications of D-peptides and D-proteins as potential therapeutic and informational tools.
2024-01-19 | PXD046228 | Pride
Project description:Mirror-image nucleosides, as potential antiviral drugs, can inhibit virus DNA polymerase to prevent virus replication. Conversely, they may be inserted into the DNA strands during DNA replication or transcription processes, leading to mutations that affect genome stability. Accumulation of significant mutation damage in cells may result in cell aging, apoptosis, and even uncontrolled cell division. We have previously explored replicative repair of mirror-image nucleosides within Escherichia coli, and this study focuses on human cells. We constructed several plasmid substrates, each carrying a specific mirror-image nucleoside, to investigate their impact on intracellular DNA replication and transcription processes. The results showed that in HepG2 cells, L-adenosine (L-dA) was the most potent substrate in inhibiting cell replication and transcription. L-cytidine (L-dC) exhibited the highest bypass efficiency in both template and non-template strands and had the most diverse mutation types. We also observed that L-dC induced immunoregulation of the JAK-STAT signaling pathway. Therefore, our results provide a theoretical basis for the disruptions caused by mirror-image nucleosides in replication and transcription and give us some understanding that mirror-image nucleoside drugs can cause cytotoxicity.
2024-08-13 | GSE274758 | GEO
Project description:Mirror-image proteins, composed of D-amino acids, are an attractive therapeutic modality, as they exhibit high metabolic stability and lack immunogenicity. Development of mirror-image binding proteins is achieved through chemical synthesis of D-target proteins, phage display library selection of L-binders and chemical synthesis of (mirror-image) D binders that consequently bind the physiological L-targets. Monobodies are well-established synthetic (L )binding proteins and their small size (~90 residues) and lack of endogenous cysteine residues make them particularly accessible to chemical synthesis. Here, we developed monobodies with nanomolar binding affinities against the D-SH2 domain of the leukemic tyrosine kinase BCR::ABL1. Two crystal structures of heterochiral monobody-SH2 complexes revealed targeting of the pY binding pocket by an unconventional binding mode. We then prepared potent D-monobodies by either ligating two chemically synthesized D-peptides or by self-assembly without ligation. Their proper folding and stability were determined and high affinity binding to the L-target was shown. D-monobodies were protease-resistant, showed long-term plasma stability, inhibited BCR::ABL1 kinase activity and bound BCR::ABL1 in cells and (to some extent in) cell lysates with high selectivity. Hence, we demonstrate that functional D monobodies can be developed readily. Our work represents an important step towards the possible future therapeutic use of D-monobodies when combined with emerging methods to enable cytoplasmic delivery of monobodies.
2024-10-28 | PXD056009 | Pride
Project description:BackgroundMirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to MIP in an animal model of CRPS-I.MethodsWe established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining, and animal behavioral assays were used to screen potential genes in the contralateral dorsal root ganglia (DRG) that may be involved in MIP.ResultsThe CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are important processes involved in pain sensitization, neuroinflammation, and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and the pain mechanism in MIP.ConclusionWe provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.
| S-EPMC8426644 | biostudies-literature
Project description:Effects of mirror-image nucleosides on DNA replication and transcription in human cells
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Project description:Six different mouse pain models were studied: (1) tumour-injection model for bone cancer pain; (2) partial sciatic nerve ligation (PSL) for neuropathic pain; (3) mechanical joint loading for osteoarthritis pain; (4) oxaliplatin-induced painful neuropathy for chemotherapy-induced pain; (5) hyperalgesic priming model for chronic muscle pain; and (6) complete Freund’s adjuvant (CFA)-injection for inflammatory pain. Transcriptomic microarray analyses were performed using RNA isolated from dorsal root ganglia.
2018-06-11 | E-MTAB-6864 | biostudies-arrayexpress
Project description:Expression profiling of L4 and L5 Dorsal Root Ganglion (DRG) in the spinal nerve ligation model of neuropathic pain. The goal of the study was to identify genes involved in neuropathic pain This series of samples comprises of contralateral and ipsilateral L4 and L5 DRG tissue collected 4 weeks after rats underwent a L5 spinal nerve ligation (SNL) or a sham operation with no L5 spinal nerve ligation. This defines 8 groups (i) contralateral L4 DRG from the sham cohort (n=5), (ii) ipsilateral L4 DRG from sham cohort (n=5), (iii) contralateral L4 DRG from SNL cohort (n=5), (iv) ipsilateral L4 DRG from the SNL chort (n=5), (v) contralateral L5 DRG from the sham cohort (n=5), (vi) ipsilateral L5 DRG from sham cohort (n=5), (vii) contralateral L5 DRG from SNL cohort (n=5), (viii) ipsilateral L5 DRG from the SNL cohort (n=5)
2011-10-17 | E-GEOD-24982 | biostudies-arrayexpress
Project description:we successfully identified pain-related genes through genome-wide expression profiling in blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p < 0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of 12 genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction. We focused on matrix metalloproteinase 9 (MMP9) that showed statistically significant difference from controls and the highest relative fold change in CRPS II patients to controls by qPCR validation (6.4 ± 2.47 times and p = 0.001). Identification of pain-related genes in peripheral blood of complex regional pain syndrome (CRPS) using cDNA microarray. Comparative gene expression profiles in peripheral blood of 5 healthy controls and 4 CRPS patients.
2013-06-06 | E-GEOD-47603 | biostudies-arrayexpress
Project description:Despite widespread use of experimental acute pain models to mimic chronic pathologies, little exploration has been undertaken on the acute pain proteome in humans. We re-solved to explore molecular alterations evoked by acute bouts of hypertonic saline (HS) induced muscle pain and map the spread of evoked mechanical hyperalgesia. This study used a 2-cohort design in healthy human participants. Cohort one (n=16) underwent in-termittent blood sampling concurrent with intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n=10) underwent bilateral sensory testing during HS infusion, to map the spread of evoked mechanical hyperalgesia. Molecular analysis in cohort one revealed a diffuse ar-ray of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Intriguingly, cohort two revealed a significant mechanical hyperalgesia which emerged in a diffuse pattern over the ipsilat-eral limb to HS-infusion. However, despite evidence of systemic molecular alterations, no such mechanical hypersensitivity was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute bouts of HS-induced muscle pain with accompanying sensory interactions.
2026-01-05 | PXD070131 | Pride