The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells in vitro

Int J Neurosci. 2022 Feb;132(2):171-180. doi: 10.1080/00207454.2020.1806266. Epub 2020 Aug 24.

Abstract

Purpose: The purpose of this study was to explore the significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the course of the differentiation of mouse bone marrow mesenchymal stem cells into Schwann-like cells in vitro.

Materials and methods: The experiment was conducted with three groups-control, TAK 165, and HRG-off. In the control group, we used the classical induction method of adding β-ME, RA, FSK, b-FGF, PDGF, and neuregulin (HRG); the cells were collected on the 7th day. Using the same basic protocol as the control group, the specific ErbB2 inhibitor mubritinib (TAK 165) was added to block the neuregulin-1/ErbB pathway in the TAK 165 group, while HRG was not added in the HRG-off group. We detected the degree of differentiation of stem cells into Schwann-like cells by using RT-PCR to examine the expression of Sox10, NRG-1, ErbB2, ErbB3, and ErbB4 and by using immunofluorescence staining to examine the Schwann cell marker S100B, Glial Fibrillary Acidic Protein (GFAP) and P75.

Results: Our results showed that the proliferation of Schwann cells was reduced and apoptosis was increased in the TAK 165 group and the HRG-off group. Sox10 was stably expressed and NRG-1, ErbB2, and ErbB3 increased in the control group. However, the expression of Sox10 in the TAK 165 group was obviously decreased at the end of induced differentiation; meanwhile, the degree of stem cell differentiation also decreased.

Conclusions: the neuregulin-1/ErbB signaling pathway plays an important role in the differentiation of bone marrow mesenchymal stem cells into Schwann-like cells and can promote the maintenance of Sox10 。.

Keywords: Mice; Sox10; bone marrow mesenchymal stem cells; differentiation; neuregulin-1/ErbB signaling pathway; schwann cells.

MeSH terms

  • Animals
  • Cell Differentiation
  • Mice
  • Neuregulin-1* / metabolism
  • Receptor, ErbB-4 / metabolism
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Schwann Cells*
  • Signal Transduction

Substances

  • Neuregulin-1
  • SOXE Transcription Factors
  • Sox10 protein, mouse
  • Receptor, ErbB-4