Guanosine-5′-triphosphate cyclohydrolase 1 regulated long noncoding RNAs are potential targets for microglial activation in neuropathic pain

Liang, Yanhu; Chen, Guowu; Li, Xuesong; Jia, Shu Fang; Meng, Chunyang

doi:10.4103/1673-5374.290914

Cited by 9 publications

(1 citation statement)

References 32 publications

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“…Previous research on microglia and NP has shown that Mapk14 is significantly upregulated and plays a role in microglial activation in NP animal models. 20 Icam1 is a glycoprotein located on the cell surface and acts as an adhesion receptor. It plays a crucial role in regulating the recruitment of white blood cells to areas of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Lou,

Xu,

Wang

et al. 2024

JPR

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Background The mechanism of Chemotherapy-induced neuropathic pain (NP) remains obscure. This study was aimed to uncover the key genes as well as protein networks that contribute to Oxaliplatin-induced NP. Material/Methods Oxaliplatin frequently results in a type of Chemotherapy-induced NP that is marked by heightened sensitivity to mechanical and cold stimuli, which can lead to intolerance and discontinuation of medication. We investigated whether these different etiologies lead to similar pathological outcomes by targeting shared genetic targets or signaling pathways. Gene expression data were obtained from the Gene Expression Comprehensive Database (GEO) for GSE38038 (representing differential expression in the spinal nerve ligation model rats) and GSE126773 (representing differential expression among the Oxaliplatin-induced NP model rats). Differential gene expression analysis was performed using GEO2R. Results Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs). Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed three shared pathways involved in both models: Kaposi sarcoma-associated herpesvirus (KSHV) infection, Epstein-Barr virus (EBV) infection, and AGE-RAGE signaling pathway in diabetic complications. Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2. Our results suggest that immune dysfunction, inflammation-related factors or regulating inflammation factors may also be related to Oxaliplatin-induced NP. Additionally, we analyzed a dataset (GSE145222) involving chronic compression of DRGs (CCD) and control groups. CCD model is a classic model for studying NP. We assessed these hub genes’ expression levels. In contrast with the control groups, the hub genes were up-regulated in CCD groups, the difference was statistically significant, except Stat1. Conclusion Our research significantly contributes to elucidating the mechanisms underlying the occurrence as well as the progression of Oxaliplatin-induced NP. We have identified crucial genes and signaling pathways associated with this condition.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Lou,

Xu,

Wang

et al. 2024

JPR

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Overexpression of miR-133a-3p reduces microglia activation by binding to GCH1, alleviating neuroinflammation and neuropathic pain

Gao,

Yang,

Shu

et al. 2024

Exp Brain Res

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Sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA2b) mediates oxidation‐induced endoplasmic reticulum stress to regulate neuropathic pain

Zhao

Tang

et al. 2022

British J Pharmacology

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Background and Purpose Neuropathic pain is a widespread health problem with limited curative treatment. Decreased sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) expression has been reported in dorsal root ganglion (DRG) of animals suffering from neuropathic pain. We aimed to establish the relationship between SERCA expression and the pain responses and to elucidate the underlying molecular mechanism. Experimental Approach Neuropathic pain was modelled using rat chronic constriction injury (CCI). Ca2+ imaging and current clamp patch‐clamp were used to determine cytosolic Ca2+ levels and action potential firing, respectively. Western blots, immunofluorescence staining and qRT‐PCR were used to quantitatively assess protein and mRNA expression, respectively. H&E staining and coupled enzyme assays were used to evaluate the nerve injury and SERCA2b activity, respectively. Key Results SERCA2b is the predominant SERCA isoform in rat DRG and its expression is decreased after CCI at mRNA, protein and activity levels. Whereas inhibiting SERCA with thapsigargin causes neuronal hyperexcitation, nerve injury, endoplasmic reticulum (ER) stress, satellite glial cell activation and mechanical allodynia, activating SERCA by CDN1163 or overexpressing SERCA2b in DRG after CCI produces long‐term relief of mechanical and thermal allodynia accompanied by morphological and functional restoration through alleviation of ER stress. Furthermore, the down‐regulation of DRG SERCA2b in CCI rats is caused by increased production of ROS through Sp1‐dependent transcriptional inhibition. Conclusion and Implications Our findings reveal a novel pathway centring around SERCA2b as the key molecule underlying the mechanism of development and maintenance of neuropathic pain, and SERCA2b activators have the potential for therapeutic treatment of neuropathic pain.

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Guanosine-5′-triphosphate cyclohydrolase 1 regulated long noncoding RNAs are potential targets for microglial activation in neuropathic pain

Cited by 9 publications

References 32 publications

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Overexpression of miR-133a-3p reduces microglia activation by binding to GCH1, alleviating neuroinflammation and neuropathic pain

Sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA2b) mediates oxidation‐induced endoplasmic reticulum stress to regulate neuropathic pain

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Guanosine-5′-triphosphate cyclohydrolase 1 regulated long noncoding RNAs are potential targets for microglial activation in neuropathic pain

Cited by 9 publications

References 32 publications

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis

Overexpression of miR-133a-3p reduces microglia activation by binding to GCH1, alleviating neuroinflammation and neuropathic pain

Sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA2b) mediates oxidation‐induced endoplasmic reticulum stress to regulate neuropathic pain

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Sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA2b) mediates oxidation‐induced endoplasmic reticulum stress to regulate neuropathic pain