Purinergic and Store-Operated Ca2+ Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration
| Autor: | Lin-Hua Jiang, Fatema Mousawi, Xuebin Yang, Joan A. Sim, Yunjie Hao, Jing Li, Sébastien Roger, Hongsen Peng, Sreenivasan Ponnambalam |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
0301 basic medicine P2Y receptor ORAI1 Protein Biology Young Adult 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Cell Movement Calcium flux Humans Calcium Signaling Stromal Interaction Molecule 1 Child Dental Pulp Tissue homeostasis Calcium signaling ORAI1 Purinergic receptor Receptors Purinergic Mesenchymal Stem Cells Cell migration Cell Biology Neoplasm Proteins Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine Female Signal transduction Extracellular Space Developmental Biology |
| Zdroj: | Stem Cells. 34:2102-2114 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2370 |
| Popis: | ATP is an extrinsic signal that can induce an increase in the cytosolic Ca2+ level ([Ca2+]c) in mesenchymal stem cells (MSCs). However, the cognate intrinsic mechanisms underlying ATP-induced Ca2+ signaling in MSCs is still contentious, and their importance in MSC migration remains unknown. In this study, we investigated the molecular mechanisms underlying ATP-induced Ca2+ signaling and their roles in the regulation of cell migration in human dental pulp MSCs (hDP-MSCs). RT-PCR analysis of mRNA transcripts and interrogation of agonist-induced increases in the [Ca2+]c support that P2X7, P2Y1, and P2Y11 receptors participate in ATP-induced Ca2+ signaling. In addition, following P2Y receptor activation, Ca2+ release-activated Ca2+ Orai1/Stim1 channel as a downstream mechanism also plays a significant role in ATP-induced Ca2+ signaling. ATP concentration-dependently stimulates hDP-MSC migration. Pharmacological and genetic interventions of the expression or function of the P2X7, P2Y1 and P2Y11 receptors, and Orai1/Stim1 channel support critical involvement of these Ca2+ signaling mechanisms in ATP-induced stimulation of hDP-MSC migration. Taken together, this study provide evidence to show that purinergic P2X7, P2Y1, and P2Y11 receptors and store-operated Orai1/Stim1 channel represent important molecular mechanisms responsible for ATP-induced Ca2+ signaling in hDP-MSCs and activation of these mechanisms stimulates hDP-MSC migration. Such information is useful in building a mechanistic understanding of MSC homing in tissue homeostasis and developing more efficient MSC-based therapeutic applications. |
| Databáze: | OpenAIRE |
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