Stichopus japonicus Polysaccharide, Fucoidan, or Heparin Enhanced the SDF-1α/CXCR4 Axis and Promoted NSC Migration via Activation of the PI3K/Akt/FOXO3a Signaling Pathway

Cell Mol Neurobiol. 2016 Nov;36(8):1311-1329. doi: 10.1007/s10571-016-0329-4. Epub 2016 Feb 17.

Abstract

Stichopus japonicus Polysaccharide (SJP) is a sulfated polysaccharide from the body wall of the sea cucumber, Stichopus japonicus. Fucoidan is a heparinoid compound that belongs to a family of sulfated polyfucose polysaccharides. Heparin is a glycosaminoglycan. SJP, fucoidan, and heparin profoundly promoted stromal cell-derived factor 1 alpha (SDF-1α)-induced neural stem cell (NSC) migration in a concentration-dependent manner. In addition, the basal migration capacity of cells was significantly promoted after incubation with SJP, fucoidan, or heparin. Interaction of SJP, fucoidan, or heparin with SDF-1α efficiently showed additive effects on the promotion of cell migration from the neurosphere. SJP, fucoidan, or heparin interaction with SDF-1α treatment could increase Nestin expression. SDF-1α modulated by SJP, fucoidan, or heparin activated the CXCR4 receptor and directed cellular migration via the activation of the PI3K/Akt/FOXO3a signaling pathway. Moreover, interaction of SJP, fucoidan, or heparin with SDF-1α effectively promoted NSC migration and induced SDF-1α and CXCR4 expressions. Results suggested that SJP, fucoidan, and heparin might be good candidates for alleviating injury-initiated signals to which NSCs respond.

Keywords: CXCR4; Fucoidan; Heparin; NSC; SDF-1α; SJP.

MeSH terms

  • Animals
  • Cell Movement* / drug effects
  • Chemokine CXCL12 / metabolism*
  • Forkhead Box Protein O3 / metabolism
  • Heparin / pharmacology
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polysaccharides / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction* / drug effects
  • Stichopus / chemistry

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Polysaccharides
  • Receptors, CXCR4
  • Heparin
  • fucoidan