TRIM32 affects the recovery of motor function following spinal cord injury through regulating proliferation of glia

Oncotarget. 2017 Jul 11;8(28):45380-45390. doi: 10.18632/oncotarget.17492.

Abstract

Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after spinal cord injury (SCI). However, the underlying molecular mechanisms remain unclear. In the present study, we identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following SCI. We further observe that deficiency of TRIM32 results in increased numbers of astrocytes and microglia, which is accompanied by enhanced proliferation of both cells and increased secretion of interleukin (IL)-1 and IL-10. The axonal regeneration is impaired in the spinal cord of TRIM32-/- mice following SCI, which is indicated by increased distances of the corticospinal tracts (CST) fiber to the lesion site and less axonal sprouting. We further show that deficiency of TRIM32 results in delay motor recovery following SCI. Therefore, TRIM32 is a novel essential positive factor modulating axonal regeneration and the recovery of motor function following SCI, possibly through suppressing proliferation of glial cells.

Keywords: axonal regeneration; glia; neuroinflammation; spinal cord injury; tripartite motif protein 32.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Axons / metabolism
  • Cell Count
  • Cell Proliferation
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Mice
  • Mice, Knockout
  • Microglia / metabolism
  • Motor Activity / genetics*
  • Nerve Regeneration / genetics
  • Neuroglia / metabolism*
  • Neurons / metabolism
  • Recovery of Function
  • Spinal Cord Injuries / etiology*
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / rehabilitation
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Cytokines
  • TRIM32 protein, mouse
  • Ubiquitin-Protein Ligases