PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT-mTOR Pathway: An In Vitro Study

J Biochem Mol Toxicol. 2024 Dec;38(12):e70063. doi: 10.1002/jbt.70063.

Abstract

This study aims to explore the role of Protein Kinase N2 (PKN2) in peripheral nerve injury (PNI) and evaluate its potential as a therapeutic target. The study employed a PC12 cell model to assess the effects of PKN2 overexpression on cell proliferation, migration, synaptic growth, and autophagic activity, with a focus on the regulatory role of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. The results demonstrated that PKN2 overexpression significantly promoted PC12 cell proliferation and cell migration, while also enhancing synaptic growth. Additionally, a significant suppression of autophagy was observed. Mechanistic analysis revealed that PKN2 inhibited autophagic activity through the activation of the AKT/mTOR pathway. In summary, PKN2 plays a significant role in peripheral nerve repair by promoting cell proliferation, migration, and synaptic growth, while inhibiting autophagy through the AKT/mTOR pathway. These findings suggest that targeting PKN2 may represent an effective therapeutic strategy for the treatment of PNI.

Keywords: AKT/mTOR; PC12 cells; Protein Kinase N2 (PKN2); autophagy; peripheral nerve injury (PNI); synaptic growth.

MeSH terms

  • Animals
  • Autophagy*
  • Cell Movement*
  • Cell Proliferation*
  • PC12 Cells
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Protein Kinase C* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Signal Transduction*
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • protein kinase N
  • Protein Kinase C
  • mTOR protein, rat