ArticleCNS neuroscience & therapeutics2018
Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats.
Article in CNS neuroscience & therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- The CXCL12/CXCR4 Axis: An Emerging Therapeutic Target for Chronic Pain.Journal of pain research · 2025Review
- Isoorientin Suppresses Invasion of Breast and Colon Cancer Cells by Inhibition of CXC Chemokine Receptor 4 Expression.Biomolecules & therapeutics · 2024Article
- Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024Review
- DNMT1 involved in the analgesic effect of folic acid on gastric hypersensitivity through downregulating ASIC1 in adult offspring rats with prenatal maternal stress.CNS neuroscience & therapeutics · 2023Article
- DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.International journal of molecular sciences · 2022Review
- ROS‑mediated hypomethylation of PRDX5 promotes STAT3 binding and activates the Nrf2 signaling pathway in NSCLC.International journal of molecular medicine · 2021Article
- The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4.BMC molecular and cell biology · 2021Article
- Integrated Analysis of Omics Data Reveal AP-1 as a Potential Regulation Hub in the Inflammation-Induced Hyperalgesia Rat Model.Frontiers in immunology · 2021Article
- Identification of Matrine as a Novel Regulator of the CXCR4 Signaling Axis in Tumor Cells.International journal of molecular sciences · 2020Article
- Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats.Journal of neuroinflammation · 2020Article
- The Role of DNA Methylation in Transcriptional Regulation of Pro-Nociceptive Genes in Rat Trigeminal Ganglia.Epigenetics insights · 2020Article
- Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats.CNS neuroscience & therapeutics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AIM AND
methodsChronic pain associated with inflammation is a common clinical problem, and the underlying mechanisms yet are incompletely defined. DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under inflammatory pain condition remain largely unknown. Here, we investigated how chemokine receptor CXCR4 expression is regulated by DNA methylation and how it contributes to inflammatory pain induced by complete Freund's adjuvant (CFA) in rats.
resultsIntraplantar injection of CFA could not only induce significant hyperalgesia in rats, but also significantly increase the expression of CXCR4 mRNA and protein in the dorsal root ganglion (DRG). Intrathecal injection of CXCR4 antagonist AMD3100 significantly relieved hyperalgesia in inflammatory rats in a time- and dose-dependent manner. Bisulfite sequencing and methylation-specific PCR demonstrate that CFA injection led to a significant demethylation of CpG island at CXCR4 gene promoter. Consistently, the expression of DNMT3b was significantly downregulated after CFA injection. Online software prediction reveals three binding sites of p65 in the CpG island of CXCR4 gene promoter, which has confirmed by the chromatin immunoprecipitation assay, CFA treatment significantly increases the recruitment of p65 to CXCR4 gene promoter. Inhibition of NF-kB signaling using p65 inhibitor pyrrolidine dithiocarbamate significantly prevented the increases of the CXCR4 expression.
conclusionUpregulation of CXCR4 expression due to promoter demethylation followed by increased recruitment of p65 to promoter of CXCR4 gene contributes to inflammatory hyperalgesia. These findings provide a theoretical basis for the treatment of chronic pain from an epigenetic perspective.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.