Upregulation of <scp>CXCR</scp>4 through promoter demethylation contributes to inflammatory hyperalgesia in rats

Li, Feng; Xue, Zhou-Ya; Yuan, Yuan; Huang, Saisai; Fan, Yihui; Zhu, Xiaohui; Wei, Lei

doi:10.1111/cns.12845

Cited by 19 publications

(32 citation statements)

References 46 publications

(75 reference statements)

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“…(A) After 24 h of CFA injection, the rats in the model group present mechanical hyperalgesia, n = 15. (B) After injection of CFA for 24 h, the PWL was also measured, which validates our old model [14].…”

Section: Resultssupporting

confidence: 78%

“…The SD rats maintained at standardized feeding environment including 12-hours shift light-dark cycle and ambient temperature of 24 ± 1 °C. The CFAinduced chronic in ammatory pain model was established by unilateral subcutaneous injection of CFA 0.1 mL at sterile foot skin and was described in our previous research [6] [14]. All experiments were approved by the Animal Research Ethics Committee from The First People's Hospital of Yancheng, Suzhou Municipal Hospital A liated to Nanjing Medical University and Nantong University.…”

Section: Animal Modelmentioning

confidence: 99%

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Multi-omics Study Reveal AP-1 as a Regulation Hub in Inflammation Induced Hyperalgesia Rat

Zhu

Feng

Wang

et al. 2020

Preprint

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Inflammation associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanism of inflammation associated chronic pain remains unclear. Complete Freund's adjuvant (CFA) induced cutaneous inflammation rat has been widely used as an inflammation-induced pain hypersensitivity model. Herein, we presented a transcriptomic profile of CFA-induced rat dorsal root ganglion via a multi-omics approach. We identified 418 differentially expressed mRNAs, 120 differentially expressed microRNAs and 2670 differentially methylated regions, which are all highly associated with multiple inflammation related pathways, including NF-κB signaling pathways and IFN signaling pathways. Multi-omics analysis further demonstrated that AP-1 network, which works as a regulator of inflammation response, is sophisticatedly regulated at both transcriptomic and epigenetic level. We believe our data will not only provide drug screening targets for treating chronic pain and inflammation, but also shed a light on the molecular network inflammation induced hyperalgesia.

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Section: Resultssupporting

confidence: 78%

Section: Animal Modelmentioning

confidence: 99%

Multi-omics Study Reveal AP-1 as a Regulation Hub in Inflammation Induced Hyperalgesia Rat

Zhu

Feng

Wang

et al. 2020

Preprint

Self Cite

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“…However, only focusing on post-transcriptional regulation is not enough to illustrate how CFA-induced in ammatory process is regulated comprehensively. In fact, our previous work has demonstrated that dysregulation of DNA methylation is involved in the CFA-induced in ammation model [14]. A recent study also described that hypomethylation of nerve growth factors affects In ammatory hyperalgesia in rats [39].…”

Section: Introductionmentioning

confidence: 95%

Integrated analysis of Transcriptomic Data Reveal AP-1 as a Potential Regulation Hub in Inflammation Induced Hyperalgesia Rat

Zhu

Wang

et al. 2020

Preprint

Self Cite

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Inflammation associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanism of inflammation associated chronic pain remains unclear. Complete Freund's adjuvant (CFA) induced cutaneous inflammation rat has been widely used as an inflammation-induced pain hypersensitivity model. Herein, we presented a transcriptomic profile of CFA-induced rat dorsal root ganglion via an approach targeting gene expression, DNA methylation and post-transcriptional regulation. We identified 418 differentially expressed mRNAs, 120 differentially expressed microRNAs and 2670 differentially methylated regions, which are all highly associated with multiple inflammation related pathways, including NF-κB signaling pathways and IFN signaling pathways. Integrated analysis further demonstrated that AP-1 network, which may work as a regulator of inflammation response, is sophisticatedly regulated at both transcriptomic and epigenetic level. We believe our data will not only provide drug screening targets for treating chronic pain and inflammation, but also shed a light on the molecular network inflammation induced hyperalgesia.

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“…Chronic pain is usually accompanied by tissue damage and inflammation. Most scholars believe that tissue damage or inflammation leads to increased release of multiple inflammatory factors or pain-related genes, and this may be an important factor for the formation and development of chronic pain [1][2][3], but the pathogenesis of chronic pain remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats

Yuan

Chen

et al. 2020

J Neuroinflammation

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Background: Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear. Methods: We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund's adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model. Results: CFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4-6 dorsal root ganglions (DRGs) in rats. Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, CFA treatment promoted binding of C/ EBPα to the NGF gene promoter region and C/EBPα siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats. Conclusion: Collectively, the results indicated that CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of C/EBPα with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.

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Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats

Abstract: Upregulation 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.

Cited by 19 publications

References 46 publications

Multi-omics Study Reveal AP-1 as a Regulation Hub in Inflammation Induced Hyperalgesia Rat

Multi-omics Study Reveal AP-1 as a Regulation Hub in Inflammation Induced Hyperalgesia Rat

Integrated analysis of Transcriptomic Data Reveal AP-1 as a Potential Regulation Hub in Inflammation Induced Hyperalgesia Rat

Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats

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