MMP24 Contributes to Neuropathic Pain in an FTO-Dependent Manner in the Spinal Cord Neurons.

ABSTRACT: Nerve injury-induced gene expression change in the spinal cord is critical for neuropathic pain genesis. RNA N⁶-methyladenosine (m⁶A) modification represents an additional layer of gene regulation. We showed that spinal nerve ligation (SNL) upregulated the expression of matrix metallopeptidase 24 (MMP24) protein, but not Mmp24 mRNA, in the spinal cord neurons. Blocking the SNL-induced upregulation of spinal MMP24 attenuated local neuron sensitization, neuropathic pain development and maintenance. Conversely, mimicking MMP24 increase promoted the spinal ERK activation and produced evoked nociceptive hypersensitivity. Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and RNA Immunoprecipitation (RIP) assay indicated the decreased m⁶A enrichment

SUBMITTER: Ma L 

PROVIDER: S-EPMC8118694 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature