Neurochemical research, 2021-08, Vol.46 (8), p.2181-2191
2021
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- Autor(en) / Beteiligte
- Titel
- ZEB1 Induces Ddr1 Promoter Hypermethylation and Contributes to the Chronic Pain in Spinal Cord in Rats Following Oxaliplatin Treatment
- Ist Teil von
- Neurochemical research, 2021-08, Vol.46 (8), p.2181-2191
- Ort / Verlag
- New York: Springer US
- Erscheinungsjahr
- 2021
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- Application of chemotherapeutic oxaliplatin represses gene transcription through induction of DNA methylation, which may contribute to oxaliplatin-induced chronic pain. Here, Ddr1 , which showed an increased methylation in the promoter, was screened from the SRA methylation database (PRJNA587622) after oxaliplatin treatment. qPCR and MeDIP assays verified that oxaliplatin treatment increased the methylation in Ddr1 promoter region and decreased the expression of DDR1 in the neurons of spinal dorsal horn. In addition, overexpression of DDR1 by intraspinal injection of AAV-hSyn-Ddr1 significantly alleviated the mechanical allodynia induced by oxaliplatin. Furthermore, we found that oxaliplatin treatment increased the expression of DNMT3b and ZEB1 in dorsal horn neurons, and promoted the interaction between DNMT3b and ZEB1. Intrathecal injection of ZEB1 siRNA inhibited the enhanced recruitment of DNMT3b and the hypermethylation in Ddr1 promoter induced by oxaliplatin. Finally, ZEB1 siRNA rescued the DDR1 downregulation and mechanical allodynia induced by oxaliplatin. In conclusion, these results suggested that the ZEB1 recruited DNMT3b to the Ddr1 promoter, which induced the DDR1 downregulation and contributed to the oxaliplatin-induced chronic pain.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0364-3190eISSN: 1573-6903DOI: 10.1007/s11064-021-03355-5Titel-ID: cdi_proquest_journals_2548029718
- Format
- –
- Schlagworte
- Animals, Biochemistry, Biomedical and Life Sciences, Biomedicine, Cell Biology, Chronic pain, Chronic Pain - chemically induced, Chronic Pain - metabolism, Deoxyribonucleic acid, Discoidin Domain Receptor 1 - genetics, DNA, DNA (Cytosine-5-)-Methyltransferases - metabolism, DNA - metabolism, DNA methylation, DNA Methylation - drug effects, DNA Methylation - physiology, DNA Methyltransferase 3B, Dorsal horn, Down-Regulation - drug effects, Hyperalgesia - chemically induced, Hyperalgesia - metabolism, Injection, Male, Neuralgia - chemically induced, Neuralgia - metabolism, Neurochemistry, Neurology, Neurons, Neurosciences, Original Paper, Oxaliplatin, Oxaliplatin - adverse effects, Pain, Pain perception, Promoter Regions, Genetic - physiology, Rats, Rats, Sprague-Dawley, RNA, Small Interfering - pharmacology, siRNA, Spinal cord, Spinal Cord Dorsal Horn - drug effects, Spinal Cord Dorsal Horn - metabolism, Transcription, Up-Regulation - drug effects, Zinc Finger E-box-Binding Homeobox 1 - metabolism