title: Purinergic and Store-Operated Ca(2+) Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration.
abstract: ATP is an extrinsic signal that can induce an increase in the cytosolic Ca(2+) level ([Ca(2+) ]c ) in mesenchymal stem cells (MSCs). However, the cognate intrinsic mechanisms underlying ATP-induced Ca(2+) 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 Ca(2+) 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 [Ca(2+) ]c support that P2X7, P2Y1 , and P2Y11 receptors participate in ATP-induced Ca(2+) signaling. In addition, following P2Y receptor activation, Ca(2+) release-activated Ca(2+) Orai1/Stim1 channel as a downstream mechanism also plays a significant role in ATP-induced Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. Stem Cells 2016;34:2102-2114.
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.|Department of Oral Biology, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom.
authors.forename: Hongsen
authors.initials: H
authors.lastname: Peng
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Hao
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Fatema
authors.initials: F
authors.lastname: Mousawi
authors.affiliation: Inserm UMR 1069, University of Tours, Tours, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Roger
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Faculty of Life Science, University of Manchester, Manchester, United Kingdom.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Sim
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Sreenivasan
authors.initials: S
authors.lastname: Ponnambalam
authors.affiliation: Department of Oral Biology, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.|Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, People's Republic of China.
authors.forename: Lin-Hua
authors.initials: LH
authors.lastname: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D020013:Calcium Signaling / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002648:Child; D003782:Dental Pulp / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D011983:Receptors, Purinergic; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D000255:Adenosine Triphosphate