KDM2B-PP1 Promotes Remyelination and Functional Recovery After Facial Nerve Injury.

BACKGROUND

Peripheral nerve injury (PNI) often causes persistent sensory and motor deficits because of incomplete axonal regeneration and insufficient remyelination. Schwann cells (SCs) are essential for peripheral nerve repair, but effective recovery depends on their timely transition from a repair state to a myelinating phenotype.

OBJECTIVE(S): To investigate whether KDM2B-PP1, a bioactive peptide designed to disrupt the interaction between lysine-specific demethylase 2B (KDM2B) and enhancer of zeste homologue 2 (EZH2), promotes SC redifferentiation, remyelination, and functional recovery after PNI.

METHODS

Primary rat SCs were treated with KDM2B-PP1 in vitro. Myelin-related gene and protein expression were assessed by PCR array, qPCR, Western blotting, and ELISA. The effects of KDM2B-PP1 on SC proliferation, apoptosis, and migration were also examined. A rat facial nerve transection model was used to evaluate the effects of local KDM2B-PP1 administration on remyelination, nerve structure, and functional recovery in vivo.

RESULTS

KDM2B-PP1 disrupted the KDM2B-EZH2 interaction and relieved EZH2-mediated repression of myelin-related genes. In SCs, KDM2B-PP1 increased the expression of myelin-associated transcripts and proteins, including Olig1, and promoted redifferentiation toward a myelinating phenotype. In vivo, local administration of KDM2B-PP1 enhanced myelin sheath formation, improved nerve architecture, and promoted late-stage functional recovery after facial nerve injury. KDM2B-PP1 did not significantly affect SC proliferation, apoptosis, or migration.

CONCLUSIONS

KDM2B-PP1 is a novel epigenetic modulator that selectively promotes SC-mediated remyelination and functional recovery after peripheral nerve injury. These findings provide new insight into the epigenetic regulation of peripheral nerve regeneration and support KDM2B-PP1 as a potential therapeutic candidate for PNI.