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Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piez...

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Autores principales: Atcha, Hamza, Jairaman, Amit, Holt, Jesse R., Meli, Vijaykumar S., Nagalla, Raji R., Veerasubramanian, Praveen Krishna, Brumm, Kyle T., Lim, Huy E., Othy, Shivashankar, Cahalan, Michael D., Pathak, Medha M., Liu, Wendy F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167181/
https://www.ncbi.nlm.nih.gov/pubmed/34059671
http://dx.doi.org/10.1038/s41467-021-23482-5
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author Atcha, Hamza
Jairaman, Amit
Holt, Jesse R.
Meli, Vijaykumar S.
Nagalla, Raji R.
Veerasubramanian, Praveen Krishna
Brumm, Kyle T.
Lim, Huy E.
Othy, Shivashankar
Cahalan, Michael D.
Pathak, Medha M.
Liu, Wendy F.
author_facet Atcha, Hamza
Jairaman, Amit
Holt, Jesse R.
Meli, Vijaykumar S.
Nagalla, Raji R.
Veerasubramanian, Praveen Krishna
Brumm, Kyle T.
Lim, Huy E.
Othy, Shivashankar
Cahalan, Michael D.
Pathak, Medha M.
Liu, Wendy F.
author_sort Atcha, Hamza
collection PubMed
description Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca(2+) reporter, Salsa6f, reveal that Ca(2+) influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.
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spelling pubmed-81671812021-06-07 Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing Atcha, Hamza Jairaman, Amit Holt, Jesse R. Meli, Vijaykumar S. Nagalla, Raji R. Veerasubramanian, Praveen Krishna Brumm, Kyle T. Lim, Huy E. Othy, Shivashankar Cahalan, Michael D. Pathak, Medha M. Liu, Wendy F. Nat Commun Article Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca(2+) reporter, Salsa6f, reveal that Ca(2+) influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses. Nature Publishing Group UK 2021-05-31 /pmc/articles/PMC8167181/ /pubmed/34059671 http://dx.doi.org/10.1038/s41467-021-23482-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Atcha, Hamza
Jairaman, Amit
Holt, Jesse R.
Meli, Vijaykumar S.
Nagalla, Raji R.
Veerasubramanian, Praveen Krishna
Brumm, Kyle T.
Lim, Huy E.
Othy, Shivashankar
Cahalan, Michael D.
Pathak, Medha M.
Liu, Wendy F.
Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title_full Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title_fullStr Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title_full_unstemmed Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title_short Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
title_sort mechanically activated ion channel piezo1 modulates macrophage polarization and stiffness sensing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167181/
https://www.ncbi.nlm.nih.gov/pubmed/34059671
http://dx.doi.org/10.1038/s41467-021-23482-5
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