Stichopus Japonicus Polysaccharide,Fucoidan,or Heparin Promotes The SDF-1α/CXCR4 Axis-induced NPC Migration

Neural progenitor cells (NPC) are self-renewing, multipotent cells that can differentiate into neurons, astrocytes and oligodendrocytes, and can provide the brain cells.Exogenous NPC transplantation and activated endogenous NPC contributes to nerve regeneration after the central nervous system disease. But the limited number of endogenous NPC, and many in the resting state, in the process of NPC transplantation, only a very small amount of NPC successfully migrate to the brain damage area, which leads to cell replacement rate is very low and limits the effect of the treatment of NPC. Therefore, it is of great significance to improve the ability of NPC migration for the application of NPC in the treatment of CNS diseases.Chemokine SDF-la binds to CXCR4, the receptor of CXCL12 on NPC, and then activates the downstream signaling pathways of SDF-1α/CXCR4 axis, which can regulate the quiescence, activation, proliferation, migration and differentiation of NPC. However, the underlying mechanism by which Stichopus japonicus Polysacchari SJP alone can significantly promote the migration of NPC in neurospheres remains poorly understood. This research to promote the migration of NPC in SJP and study its mechanism of action, and Fucoidan and Heparin as reference. The main methods and results are as follows:1. Effects of SJP, fucoidan and heparin alone or together with SDF-1α on the migration of NPCNPC was obtained from the cerebral cortex of 14-dayembryonic Wistar rats, then identified by immunocytochemical identification method. Nestin and BrdU identification showed that neurospheres were Nestin-positive and self-renewing. Cell differentiation by induction confirmed that the cells could differentiate into TUJ-1-positive neurons and GFAP-positive astrocytes, which indicated that the cells had multipotency capacity. Together, these results proved the cells were NPC. Transwell assay and neurosphere migration assay are used to detect the ability of NPC migration. The results suggested that the synergistic action of SJP, Fucoidan or Heparin and SDF-1α promoted the migration ability of NPC.2. Potential signaling pathways of SJP, fucoidan and heparin alone or together with SDF-1α in NPC migrationImmunocytochemical method and Western Blot analysis showed that the expression changes of related proteins following SJP, fucoidan and heparin alone or together with SDF-1α. SJP, fucoidan and heparin alone or together with SDF-1α improved the expression levels of SDF-1 a and its receptor CXCR4, and the effects were abolished by PI3K inhibitor (LY294002). The results showed that SJP, Fucoidan or Heparin enhanced SDF-1α/CXCR4 biological axis. SJP, fucoidan and heparin alone or together with SDF-1α improved the level of p-Akt and p-FOXO3a in NPC, and the effects were abolished by LY294002. NPC radial migration assay detected that SJP, fucoidan and heparin alone or and together with SDF-la promoted the migration of NPC, and the effects were eliminated by LY294002. In summary, SJP, fucoidan and heparin alone or and together with SDF-la promoted the SDF-1α/CXCR4 axis-induced NPC migration via the PI3K/Akt/FOXO3a signaling pathways.