Mousawi, F orcid.org/0000-0003-2267-2652, Peng, H, Li, J et al. (5 more authors) (2020) Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling. Stem Cells, 38 (3). pp. 410-421. ISSN 1066-5099
Abstract
Here we examined the Ca2+‐permeable Piezo1 channel, a newly‐identified mechanosensing ion channel, in human dental pulp‐derived mesenchymal stem cells (MSC) and hypothesized that activation of the Piezo1 channel regulates MSC migration via inducing ATP release and activation of the P2 receptor purinergic signalling. The Piezo1 mRNA and protein were readily detected in hDP‐MSC from multiple donors and, consistently, brief exposure to Yoda1, the Piezo1 channel‐specific activator, elevated intracellular Ca2+ concentration. Yoda1‐induced Ca2+ response was inhibited by ruthenium red or GsMTx4, two Piezo1 channel inhibitors, and also by Piezo1‐specific siRNA. Brief exposure to Yoda1 also induced ATP release. Persistent exposure to Yoda1 stimulated MSC migration, which was suppressed by Piezo1‐specific siRNA, and also prevented by apyrase, an ATP scavenger, or PPADS, a P2 generic antagonist. Furthermore, stimulation of MSC migration induced by Yoda1 as well as ATP was suppressed by PF431396, a PYK2 kinase inhibitor, or U0126, an inhibitor of the mitogen‐activated protein kinase MEK/ERK signaling pathway. Collectively, these results suggest that activation of the Piezo1 channel stimulates MSC migration via inducing ATP release and subsequent activation of the P2 receptor purinergic signalling and downstream PYK2 and MEK/ERK signaling pathways, thus revealing novel insights into the molecular and signalling mechanisms regulating MSC migration. Such findings provide useful information for evolving a full understanding of MSC migration and homing and developing strategies to improve MSC‐based translational applications.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
Keywords: | ATP release; MEK/ERK; P2 receptor; Piezo1 channel; PYK2 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cardiovascular Science (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Dec 2019 12:27 |
Last Modified: | 25 Jun 2023 21:58 |
Status: | Published |
Publisher: | AlphaMed Press |
Identification Number: | 10.1002/stem.3114 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:150344 |