LncRNA-PCat19 acts as a ceRNA of miR-378a-3p to facilitate microglia activation and accelerate chronic neuropathic pain in rats by promoting KDM3A-mediated BDNF demethylation
Abstract
The pathogenesis of neuropathic pain (NP) is complex, and there are various pathological processes. Previous studies have suggested that lncRNA PCAT19 is abnormally expressed in NP conduction and affects the occurrence and development of pain. The aim of this study is to analyze the role and mechanism of PCAT19 in NP induced by chronic compressive nerve injury (CCI) in mice. In this study, C57BL/6 mice were applied to establish the CCI model. sh-PCAT19 was intrathecally injected once a day for 5 consecutive days from the second day after surgery. We discovered that PCat19 level was gradually up-regulated with the passage of modeling time. Downregulation of Iba-1-positive expression, M1/M2 ratio of microglia, and pro-inflammatory factors in the spinal cords of CCI-mice after PCat19 knock-downed was observed. Mechanically, the expression of miR-378a-3p was negatively correlated with KDM3A and PCat19. Deletion of KDM3A prevented H3K9me2 demethylation of BDNF promoter and suppressed BDNF expression. Further, KDM3A promotes CCI-induced neuroinflammation and microglia activation by mediating Brain-derived neurotrophic factor (BDNF) demethylation. Together, the results suggest that PCat19 may be involved in the development of NP and that PCat19 shRNA injection can attenuate microglia-induced neuroinflammation by blocking KDM3A-mediated demethylation of BDNF and BDNF release.
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- Authors
- Zhao, Z., Zheng, X., Wang, H., Guo, J., Liu, R., Yang, G., & Huo, M.
- Affiliations
- Shaanxi Provincial People's Hospital (CN)
- Corresponding author
- Huo, Miao
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 170
- Pages
- 88-98
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W4394975728
- Semantic Scholar
- b0b8e7dff71e32a5c049b28da02ecba3e3fedfd3
- Cited by
- 11
- References
- 33
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 1
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- miR-378a-3p, KDM3A, chronic neuropathic pain, microglial activation, neuroinflammation, H3K9me2 demethylation, brain-derived neurotrophic factor, competing endogenous RNA
- MeSH terms
- Demethylation, RNA, Competitive Endogenous, Animals, Disease Models, Animal, Male, Mice, Inbred C57BL, Neuralgia, Microglia, Brain-Derived Neurotrophic Factor, MicroRNAs, Mice, Jumonji Domain-Containing Histone Demethylases, Chronic Pain, RNA, Long Noncoding
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