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A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression.
- Source :
-
Journal of Clinical Investigation . Jul2022, Vol. 132 Issue 13, p1-17. 17p. - Publication Year :
- 2022
-
Abstract
- Maladaptive changes of nerve injury-associated genes in dorsal root ganglia (DRGs) are critical for neuropathic pain genesis. Emerging evidence supports the role of long noncoding RNAs (lncRNAs) in regulating gene transcription. Here we identified a conserved lncRNA, named nerve injury-specific lncRNA (NIS-lncRNA) for its upregulation in injured DRGs exclusively in response to nerve injury. This upregulation was triggered by nerve injury-induced increase in DRG ELF1, a transcription factor that bound to the NIS-lncRNA promoter. Blocking this upregulation attenuated nerve injury-induced CCL2 increase in injured DRGs and nociceptive hypersensitivity during the development and maintenance periods of neuropathic pain. Mimicking NIS-lncRNA upregulation elevated CCL2 expression, increased CCL2-mediated excitability in DRG neurons, and produced neuropathic pain symptoms. Mechanistically, NIS-lncRNA recruited more binding of the RNA-interacting protein FUS to the Ccl2 promoter and augmented Ccl2 transcription in injured DRGs. Thus, NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathic pain management. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 132
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 157803456
- Full Text :
- https://doi.org/10.1172/JCI153563