ATP-induced Ca(2+)-signalling mechanisms in the regulation of mesenchymal stem cell migration.
ATP-induced Ca(2+)-signalling mechanisms in the regulation of mesenchymal stem cell migration.
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DOI：
10.1007/s00018-017-2545-6
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Roger S
中科院分区：
文献类型：
--
作者：
Jiang LH;Mousawi F;Yang X;Roger S
细胞迁移到指定组织或病变的能力对于组织形态发生、稳态和免疫反应的生理过程以及基于干细胞的再生医学至关重要。胞浆Ca 2+是控制和调节包括细胞迁移在内的广泛细胞功能的主要第二信使。细胞外ATP与细胞表面上的同源受体、配体门控离子通道P2 X受体和G蛋白偶联P2 Y受体的子集一起代表常见的自分泌和/或旁分泌Ca 2+信号传导机制。P2 X受体离子通道介导细胞外Ca 2+内流，而P2 Y受体的刺激触发内质网（ER）的细胞内Ca 2+释放，因此两种类型受体的激活可以升高细胞溶质Ca 2+浓度（[Ca 2 +]c），尽管具有不同的动力学和能力。P2 Y受体激活后ER Ca 2+水平的降低可进一步诱导钙池操作的Ca 2+内流，作为一种独特的Ca 2+内流途径，有助于ATP诱导的[Ca 2 +]c增加。间充质干细胞（MSC）是一组从成体组织中生长的多能干细胞，在组织工程和基于细胞的治疗中具有很好的应用前景，可治疗多种疾病。越来越多的证据表明，从干细胞本身或附近的成熟细胞中释放组成性或诱发性ATP。本文就ATP的释放和清除机制、参与ATP诱导的Ca 2+信号传导的受体和离子通道以及这些信号传导机制在ATP诱导的MSC迁移调控中的作用进行综述。
The ability of cells to migrate to the destined tissues or lesions is crucial for physiological processes from tissue morphogenesis, homeostasis and immune responses, and also for stem cell-based regenerative medicines. Cytosolic Ca2+ is a primary second messenger in the control and regulation of a wide range of cell functions including cell migration. Extracellular ATP, together with the cognate receptors on the cell surface, ligand-gated ion channel P2X receptors and a subset of G-protein-coupled P2Y receptors, represents common autocrine and/or paracrine Ca2+ signalling mechanisms. The P2X receptor ion channels mediate extracellular Ca2+ influx, whereas stimulation of the P2Y receptors triggers intracellular Ca2+ release from the endoplasmic reticulum (ER), and activation of both type of receptors thus can elevate the cytosolic Ca2+ concentration ([Ca2+]c), albeit with different kinetics and capacity. Reduction in the ER Ca2+ level following the P2Y receptor activation can further induce store-operated Ca2+ entry as a distinct Ca2+ influx pathway that contributes in ATP-induced increase in the [Ca2+]c. Mesenchymal stem cells (MSC) are a group of multipotent stem cells that grow from adult tissues and hold promising applications in tissue engineering and cell-based therapies treating a great and diverse number of diseases. There is increasing evidence to show constitutive or evoked ATP release from stem cells themselves or mature cells in the close vicinity. In this review, we discuss the mechanisms for ATP release and clearance, the receptors and ion channels participating in ATP-induced Ca2+ signalling and the roles of such signalling mechanisms in mediating ATP-induced regulation of MSC migration.
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