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Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing

The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic...

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Autores principales: Emig, Ramona, Knodt, Wiebke, Krussig, Mario J., Zgierski-Johnston, Callum M., Gorka, Oliver, Groß, Olaf, Kohl, Peter, Ravens, Ursula, Peyronnet, Rémi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002259/
https://www.ncbi.nlm.nih.gov/pubmed/33809739
http://dx.doi.org/10.3390/cells10030663
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author Emig, Ramona
Knodt, Wiebke
Krussig, Mario J.
Zgierski-Johnston, Callum M.
Gorka, Oliver
Groß, Olaf
Kohl, Peter
Ravens, Ursula
Peyronnet, Rémi
author_facet Emig, Ramona
Knodt, Wiebke
Krussig, Mario J.
Zgierski-Johnston, Callum M.
Gorka, Oliver
Groß, Olaf
Kohl, Peter
Ravens, Ursula
Peyronnet, Rémi
author_sort Emig, Ramona
collection PubMed
description The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic tissue is excessive accumulation of extracellular matrix, leading to increased tissue stiffness. Cells are known to respond to changes in their mechanical environment, but the molecular mechanisms underlying this ability are incompletely understood. We used cell culture systems and hydrogels with tunable stiffness, combined with advanced biophysical and imaging techniques, to elucidate the roles of the stretch-activated channel Piezo1 in human atrial fibroblast mechano-sensing. Changing the expression level of Piezo1 revealed that this mechano-sensor contributes to the organization of the cytoskeleton, affecting mechanical properties of human embryonic kidney cells and human atrial fibroblasts. Our results suggest that this response is independent of Piezo1-mediated ion conduction at the plasma membrane, and mediated in part by components of the integrin pathway. Further, we show that Piezo1 is instrumental for fibroblast adaptation to changes in matrix stiffness, and that Piezo1-induced cell stiffening is transmitted in a paracrine manner to other cells by a signaling mechanism requiring interleukin-6. Piezo1 may be a new candidate for targeted interference with cardiac fibroblast function.
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spelling pubmed-80022592021-03-28 Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing Emig, Ramona Knodt, Wiebke Krussig, Mario J. Zgierski-Johnston, Callum M. Gorka, Oliver Groß, Olaf Kohl, Peter Ravens, Ursula Peyronnet, Rémi Cells Article The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic tissue is excessive accumulation of extracellular matrix, leading to increased tissue stiffness. Cells are known to respond to changes in their mechanical environment, but the molecular mechanisms underlying this ability are incompletely understood. We used cell culture systems and hydrogels with tunable stiffness, combined with advanced biophysical and imaging techniques, to elucidate the roles of the stretch-activated channel Piezo1 in human atrial fibroblast mechano-sensing. Changing the expression level of Piezo1 revealed that this mechano-sensor contributes to the organization of the cytoskeleton, affecting mechanical properties of human embryonic kidney cells and human atrial fibroblasts. Our results suggest that this response is independent of Piezo1-mediated ion conduction at the plasma membrane, and mediated in part by components of the integrin pathway. Further, we show that Piezo1 is instrumental for fibroblast adaptation to changes in matrix stiffness, and that Piezo1-induced cell stiffening is transmitted in a paracrine manner to other cells by a signaling mechanism requiring interleukin-6. Piezo1 may be a new candidate for targeted interference with cardiac fibroblast function. MDPI 2021-03-16 /pmc/articles/PMC8002259/ /pubmed/33809739 http://dx.doi.org/10.3390/cells10030663 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Emig, Ramona
Knodt, Wiebke
Krussig, Mario J.
Zgierski-Johnston, Callum M.
Gorka, Oliver
Groß, Olaf
Kohl, Peter
Ravens, Ursula
Peyronnet, Rémi
Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title_full Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title_fullStr Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title_full_unstemmed Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title_short Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing
title_sort piezo1 channels contribute to the regulation of human atrial fibroblast mechanical properties and matrix stiffness sensing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002259/
https://www.ncbi.nlm.nih.gov/pubmed/33809739
http://dx.doi.org/10.3390/cells10030663
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