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Updated: Jun 10, 2026
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Published on: September 13, 2018
Targeting Dnmt3a/m5C/RelA Axis Attenuates Microglia Inflammatory Response and Improves Postoperative Recovery in
Tianyu Qin1,2, Yuan Jiang1,2,3, Yongheng Xie1,2
1Division of Spine, Department of Orthopedics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
None:
Chronic compressive cervical spinal cord injury (cCSCI) is a major cause of adult spinal cord dysfunction. Surgical decompression is the primary treatment; however, microglia-driven neuroinflammation often hampers postoperative recovery. This study was conducted to investigate the role of 5-methylcytosine (m5C) in sustaining pro-inflammatory microglial states following decompression. Using a mouse cCSCI model, we performed single-nucleus RNA sequencing (snRNA-seq) to map microglial states, calculated an m5C-regulator activity score, and validated m5C changes via dot blot. We examined the Dnmt3a-RelA pathway in primary microglia through siRNA knockdown, m5C-RIP, and mRNA stability assays. Therapeutic potential was assessed with intrathecal AAV-shDnmt3a. SnRNA-seq revealed a dominant pro-inflammatory microglial subpopulation (C1) post-decompression, enriched for NF-κB signaling. The C1 subset exhibited an elevated m5C score and increased Dnmt3a expression. Dnmt3a knockdown reduced m5C enrichment on RelA transcripts, destabilized RelA mRNA, and suppressed NF-κB activation. In vitro, Dnmt3a silencing reduced pro-inflammatory marker expression and cytokine release, and microglia-targeted AAV-shDnmt3a improved neurological recovery in cCSCI mice. These findings underscore the potential of targeting the microglia Dnmt3a/m5C/RelA axis to enhance postoperative recovery.
