基质细胞衍生因子-1α对间充质干细胞迁移的影响

Effect of SDF-1α on the migration of mesenchymal stem cells

目的:研究基质细胞衍生因子-1α(stromal cell-derived factor-1α,SDF-1α)对间充质干细胞(mesenchymal stem cells,MSCs)迁移的影响及可能的机制。方法:采用全骨髓法体外分离培养并扩增大鼠骨髓来源的MSCs,应用Boyden趋化小室实验观察不同质量浓度(0,5,25,50和100 ng/mL)的SDF-1α对MSCs定向迁移的影响,通过蛋白质印迹法和Boyden趋化小室实验观察细胞内PI3K/Akt和MAPKs信号通路在MSCs向SDF-1α迁移过程中的变化。结果:不同质量浓度的SDF-1α通过调节PI3K/Akt和MAPKs信号通路,不同程度上影响MSCs的趋化性迁移,低质量浓度的SDF-1α促进细胞迁移,而高质量浓度对细胞迁移起到抑制作用;阻断MSCs中基底水平PI3K/Akt和MAPKs信号通路在不同程度上抑制了MSCs趋向SDF-1α迁移作用。结论:MSCs向SDF-1α迁移能力随着PI3K/Akt信号的强弱而增减;JNK/SAPK信号的减弱显著抑制了SDF-1α诱导的MSCs定向迁移;SDF-1α可以促进细胞内ERK1/2和p38MAPK两条信号通路,而ERK1/2和p38MAPK信号对SDF-1α促进的细胞迁移影响并不显著。

Objective:To investigate the effect of stromal cell-derived factor-1α (SDF-1α) on the migration of mesenchymal stem cells (MSCs) and the mechanism involved in cell migration.Methods:MSCs were isolated from rat bone marrow in vitro.Boyden chamber was used to study the behavior of cell migration toward SDF-1α at different concentrations (0,5,25,50,and 100 ng/mL).Then,we detected the phosphorylation of PI3K/Akt and MAPKs by addition of SDF-1α by Western blot.Finally,pretreatment with specific chemical inhibitors to block PI3K/Akt or MAPKs signaling,we analyzed the influence of these signaling on SDF-1 α-induced cell migration by Boyden chamber.Results:SDF-1α at different concentrations influenced MSCs migration by the regulation of PI3K/Akt and MAPKs signaling,and low concentrations of SDF-1α were positive related to cell migration,while high concentrations played converse effect.Interference with basal PI3K/Akt or MAPKs signaling decreased SDF-1 α-induced MSCs migration to a variable extent.Conclusion:SDF-1α-induced MSCs migration was positively regulated to the changing of PI3K/Akt signaling.Meanwhile,blocking JNK/SAPK signaling significantly decreased SDF-1 α-induced directed migration of MSCs.Treatment with SDF-1α could promote ERK1/2 and p38MAPK signaling pathways in MSCs,yet interference with the two signaling had no significant inhibition of cell migration.