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

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机构: [1]The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu,People’s Republic of China [2]Department of Pain Medicine, Nantong Hospitalof Traditional Chinese Medicine, Nantong 226001, Jiangsu, People’s Republicof China [3]Department of Anesthesiology, Shenzhen University ClinicalMedical Academy, Shenzhen University General Hospital, Shenzhen 518055,Guangdong, People’s Republic of China [4]Department of Radiology, NantongHospital of Traditional Chinese Medicine, Nantong 226001, Jiangsu, People’sRepublic of China
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关键词: NGF C/EBPα Inflammatory pain DNA methylation Epigenetics

摘要:
Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear. 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. 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. 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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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 神经科学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 免疫学 1 区 神经科学
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出版当年[2018]版:
Q1 IMMUNOLOGY Q1 NEUROSCIENCES
最新[2023]版:
Q1 IMMUNOLOGY Q1 NEUROSCIENCES

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第一作者机构: [1]The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu,People’s Republic of China [2]Department of Pain Medicine, Nantong Hospitalof Traditional Chinese Medicine, Nantong 226001, Jiangsu, People’s Republicof China
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