IGFBP-7 inhibits the differentiation of oligodendrocyte precursor cells via regulation of Wnt/β-Catenin signaling

J Cell Biochem. 2018 Jun;119(6):4742-4750. doi: 10.1002/jcb.26654. Epub 2018 Feb 28.

Abstract

Oligodendrocytes (OLs) are glial cells that form myelin sheaths in the central nervous system. Myelin sheath plays important role in nervous system and loss of it in neurodegenerative diseases can lead to impairment of movement. Understanding the signals and factors that regulate OL differentiation can help to address novel strategies for improving myelin repair in neurodegenerative diseases. The aim of this study was to investigate the role of insulin-like growth factor-binding proteins 7 (IGFBP-7) in differentiating OL precursor cells (OPCs). It was found that oligodendrocyte precursors undergoing differentiation were accompanied by selective expression of IGFBP-7. In addition, knockdown of IGFBP-7 promoted differentiation of oligodendrocytes and increased formation of myelin in cultured cells. In contrast, excessive expression of IGFBP-7 inhibited differentiation of oligodendrocytes. Furthermore, overexpression of IGFBP-7 in oligodendrocyte precursor cells increased transcription of Wnt target genes and promoted β-Catenin nuclear translocation. These findings suggest that IGFBP-7 negatively regulates differentiation of oligodendrocyte precursor cells via regulation of Wnt/β-Catenin signaling.

Keywords: IGFBP-7; Wnt/β-Catenin; differentiation; oligodendrocytes.

MeSH terms

  • Animals
  • Cell Differentiation*
  • Gene Expression Regulation*
  • HEK293 Cells
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / biosynthesis*
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Insulin-Like Growth Factor Binding Proteins
  • beta Catenin
  • insulin-like growth factor binding protein-related protein 1