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Sphingosine-1-phosphate/S1P Receptors Signaling Modulates Cell Migration in Human Bone Marrow-Derived Mesenchymal Stem Cells

机译:鞘氨醇-1-磷酸/ S1P受体信号调节人类骨髓源间充质干细胞中的细胞迁移。

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摘要

The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a Gi/extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.
机译:将骨髓来源的间充质干细胞(BMSC)募集到受损的组织和炎症部位是临床治疗的重要步骤。但是,调节这些细胞运动的信号仍未完全了解。 1-磷酸鞘氨醇(S1P)是一种具有生物活性的鞘脂代谢产物,已知对各种细胞具有多种生物学作用。在这里,我们调查了S1P和S1P受体(S1PRs)在人类骨髓间充质干细胞迁移中的作用。我们发现S1P对人类骨髓间充质干细胞发挥了强大的迁移作用。此外,通过采用RNA干扰技术和药理学工具,我们证明S1PR1和S1PR3负责S1P诱导的人类BMSC迁移。相反,S1PR2介导迁移的抑制。此外,我们探索了S1P / S1PRs轴的下游信号传导途径,并发现S1PR1或S1PR3的激活通过Gi /细胞外调控蛋白激酶1 / 2-(ERK1 / 2-)依赖性途径增加了人类BMSC的迁移,而激活S1PR2的表达降低了通过Rho / Rho相关蛋白激酶(ROCK)途径的迁移。总之,我们揭示了S1P / S1PRs信号轴通过双向机制调节人BMSC的迁移。因此,S1PR对人BMSC活性的选择性调节可为免疫疗法或组织再生提供有效的方法。

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