Abstract
It is well-known that extracellular ATP acts as an autocrine/paracrine signal to regulate cell functions by inducing intracellular Ca2+ signalling through its cognate receptors, namely, the ligand-gated ion channel P2X receptors that mediate Ca2+ influx and/or the Gq/11-coupled P2Y receptors that link to Ca2+ release from the ER. The reduction in ER Ca2+ can trigger further extracellular Ca2+ entry by activating the store-operated Ca2+ (SOC) channel. Mesenchymal stem cells (MSC) play an important role in the homeostasis of residing tissues and have promising applications in regenerative medicines. MSC can release ATP spontaneously or in response to diverse stimuli, and express multiple P2X and Gq/11-coupled P2Y receptors that participate in ATP-induced Ca2+ signalling and regulate cell function. There is increasing evidence to show the contribution of the SOC channel in ATP-induced Ca2+ signalling in MSC. In this mini-review, we discuss the current understanding of the expression of the SOC channel in MSC and its potential role in mediating ATP-induced Ca2+ signalling and regulation of MSC differentiation, proliferation and migration.
Highlights
ATP represents one extracellular signal that regulates Mesenchymal stem cells (MSC) differentiation, proliferation, migration and tissue homing [75,76,77,78,79,80,81,82,83]
store-operated Ca2+ (SOC) channel activation or store-operated Ca2+ entry (SOCE) can be readily induced by depleting the ER Ca2+ using thapsigargin (TG) to block the sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA) that mediates Ca2+ uptake from the cytosol into the ER (Fig. 1A), circumventing the need for activating the Gq/11-phospholipase C (PLC)-IP3 receptor (IP3R) pathway
As the Ca2+-release-activated Ca2+ (CRAC) channel made of Orai1 and Stim1 represents the SOC channel with the best-established protein components and activation mechanism, we have further examined the expression of Orai1, Stim1 and Stim2, and their roles in ATP-induced Ca2+ signalling in human DP-MSC [80]
Summary
Extracellular ATP has been shown as an autocrine/paracrine signal that induces Ca2+ signaling in MSC via the P2X receptors that mediate Ca2+ influx and/or the Gq/11-coupled P2Y receptors that lead to ER Ca2+ release to stimulate Ca2+-dependent downstream signal pathways and thereby regulates cell proliferation, migration and differentiation. More research efforts are clearly required to better understand the role of the SOC/CRAC channel in ATP-induced Ca2+ signalling in MSC and regulation of cell function by physical, chemical and biological stimuli or signals known to induce ATP release and activation of the P2Y-Gq/11-PLC-IP3R pathway. Such information is useful to the utilisation of MSC in regenerative medicines and to the improvement of our knowledge about basic MSC biology
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