Exendin-4 promotes actin cytoskeleton rearrangement and protects cells from Nogo-A-Δ20 mediated spreading inhibition and growth cone collapse by down-regulating RhoA expression and activation via the PI3K pathway

Biomed Pharmacother. 2019 Jan:109:135-143. doi: 10.1016/j.biopha.2018.10.008. Epub 2018 Nov 2.

Abstract

Exendin-4 is a protein of the GLP-1 family currently used to treat diabetes. Recently, a greater number of biological properties have been associated with the GLP-1 family. Our data shows that exendin-4 treatment significantly increases the cytoskeleton rearrangement, which leads to an increasingly differentiated phenotype and reduced cell migration. We also found that exendin-4 could prevent SH-SY5Y and PC12 cells from Nogo-A-Δ20 mediated spreading inhibition and neurite collapse. Western blot analysis indicated that exendin-4 treatment both reduced the expression and activation of RhoA via the PI3K signaling pathway. These data suggest that exendin-4 may protect nerve regeneration by preventing the inhibition of Nogo-A via down-regulating RhoA expression and activation.

Keywords: Cell migration; Cell spreading; Exendin-4; Growth cone; Nogo-A-Δ20; RhoA.

MeSH terms

  • Actin Cytoskeleton / drug effects*
  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Down-Regulation
  • Exenatide / metabolism
  • Exenatide / pharmacology*
  • Growth Cones / pathology
  • Humans
  • Nerve Regeneration / drug effects
  • Neurites / pathology
  • Neuroblastoma / pathology
  • Nogo Proteins / metabolism*
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • rhoA GTP-Binding Protein / genetics*

Substances

  • Nogo Proteins
  • Exenatide
  • Phosphatidylinositol 3-Kinases
  • rhoA GTP-Binding Protein