ERK1/2 pathway-mediated differentiation of IGF-1-transfected spinal cord-derived neural stem cells into oligodendrocytes

PLoS One. 2014 Aug 27;9(8):e106038. doi: 10.1371/journal.pone.0106038. eCollection 2014.

Abstract

Spinal cord injury (SCI) is a devastating event that causes substantial morbidity and mortality, for which no fully restorative treatments are available. Stem cells transplantation offers some promise in the restoration of neurological function but with limitations. Insulin-like growth factor 1 (IGF-1) is a well-appreciated neuroprotective factor that is involved with various aspects of neural cells. Herein, the IGF-1 gene was introduced into spinal cord-derived neural stem cells (NSCs) and expressed steadily. The IGF-1-transfected NSCs exhibited higher viability and were promoted to differentiate into oligodendrocytes. Moreover, the most possible underlying mechanism, through which IGF-1 exerted its neuroprotective effects, was investigated. The result revealed that the differentiation was mediated by the IGF-1 activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and its downstream pathway. These findings provide the evidence for revealing the therapeutic merits of IGF-1-modified NSCs for SCI.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Pregnancy
  • Primary Cell Culture
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • Transfection

Substances

  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Insulin-Like Growth Factor I
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Grants and funding

The authors have no support or funding to report.