Expression of Dixdc1 and its Role in Astrocyte Proliferation after Traumatic Brain Injury

Cell Mol Neurobiol. 2017 Aug;37(6):1131-1139. doi: 10.1007/s10571-016-0446-0. Epub 2016 Nov 21.

Abstract

DIX domain containing 1 (Dixdc1), a positive regulator of Wnt signaling pathway, is recently reported to play a role in the neurogenesis. However, the distribution and function of Dixdc1 in the central nervous system (CNS) after brain injury are still unclear. We used an acute traumatic brain injury (TBI) model in adult rats to investigate whether Dixdc1 is involved in CNS injury and repair. Western blot analysis and immunohistochemistry showed a time-dependent up-regulation of Dixdc1 expression in ipsilateral cortex after TBI. Double immunofluorescent staining indicated a colocalization of Dixdc1 with astrocytes and neurons. Moreover, we detected a colocalization of Ki-67, a cell proliferation marker with GFAP and Dixdc1 after TBI. In primary cultured astrocytes stimulated with lipopolysaccharide, we found enhanced expression of Dixdc1 in parallel with up-regulation of Ki-67 and cyclin A, another cell proliferation marker. In addition, knockdown of Dixdc1 expression in primary astrocytes with Dixdc1-specific siRNA transfection induced G0/G1 arrest of cell cycle and significantly decreased cell proliferation. In conclusion, all these data suggest that up-regulation of Dixdc1 protein expression is potentially involved in astrocyte proliferation after traumatic brain injury in the rat.

Keywords: Astrocyte proliferation; Dixdc1; Rat; Traumatic brain injury.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology*
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology*
  • Cell Proliferation
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ki-67 Antigen / metabolism
  • Male
  • Neurons / metabolism
  • Neurons / pathology
  • Rats, Sprague-Dawley
  • Up-Regulation

Substances

  • Dixdc1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen