Institute of Cytology of the Russian Academy of Science, Saint-Petersburg, Russia.
J Cell Mol Med. 2020 Apr;24(8):4580-4588. doi: 10.1111/jcmm.15115. Epub 2020 Mar 9.
Extracellular ATP through the activation of the P2X and P2Y purinergic receptors affects the migration, proliferation and differentiation of many types of cells, including stem cells. High plasticity, low immunogenicity and immunomodulation ability of mesenchymal stem cells derived from human endometrium (eMSCs) allow them to be considered a prominent tool for regenerative medicine. Here, we examined the role of ATP in the proliferation and migration of human eMSCs. Using a wound healing assay, we showed that ATP-induced activation of purinergic receptors suppressed the migration ability of eMSCs. We found the expression of one of the ATP receptors, the P2X receptor in eMSCs. In spite of this, cell activation with specific P2X receptor agonist, BzATP did not significantly affect the cell migration. The allosteric P2X receptor inhibitor, AZ10606120 also did not prevent ATP-induced inhibition of cell migration, confirming that inhibition occurs without P2X receptor involvement. Flow cytometry analysis showed that high concentrations of ATP did not have a cytotoxic effect on eMSCs. At the same time, ATP induced the cell cycle arrest, suppressed the proliferative and migration capacity of eMSCs and therefore could affect the regenerative potential of these cells.
细胞外 ATP 通过激活 P2X 和 P2Y 嘌呤能受体影响包括干细胞在内的多种细胞的迁移、增殖和分化。来源于人子宫内膜的间充质干细胞（eMSCs）具有高可塑性、低免疫原性和免疫调节能力，使其成为再生医学的重要工具。在这里，我们研究了 ATP 在人 eMSCs 增殖和迁移中的作用。通过划痕实验，我们表明 ATP 诱导的嘌呤能受体激活抑制了 eMSCs 的迁移能力。我们发现 eMSCs 中表达一种 ATP 受体，即 P2X 受体。尽管如此，用特异性 P2X 受体激动剂 BzATP 激活细胞并没有显著影响细胞迁移。别构 P2X 受体抑制剂 AZ10606120 也不能阻止 ATP 诱导的细胞迁移抑制，这证实了抑制作用的发生与 P2X 受体无关。流式细胞术分析表明，高浓度的 ATP 对 eMSCs 没有细胞毒性作用。同时，ATP 诱导细胞周期停滞，抑制 eMSCs 的增殖和迁移能力，从而可能影响这些细胞的再生潜力。
