Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling
Fibrotic tissues share many common features with neoplasms where there is an increased stiffness of the extracellular matrix (ECM). In this review, we present recent discoveries related to the role of the mechanosensitive ion channel Piezo1 in several diseases, especially in regulating tumor progres...
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MDPI AG
2022-07-01
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Online Access: | https://www.mdpi.com/1422-0067/23/15/8065 |
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author | Nicoletta Braidotti Suet Nee Chen Carlin S. Long Dan Cojoc Orfeo Sbaizero |
author_facet | Nicoletta Braidotti Suet Nee Chen Carlin S. Long Dan Cojoc Orfeo Sbaizero |
author_sort | Nicoletta Braidotti |
collection | DOAJ |
description | Fibrotic tissues share many common features with neoplasms where there is an increased stiffness of the extracellular matrix (ECM). In this review, we present recent discoveries related to the role of the mechanosensitive ion channel Piezo1 in several diseases, especially in regulating tumor progression, and how this can be compared with cardiac mechanobiology. Based on recent findings, Piezo1 could be upregulated in cardiac fibroblasts as a consequence of the mechanical stress and pro-inflammatory stimuli that occurs after myocardial injury, and its increased activity could be responsible for a positive feedback loop that leads to fibrosis progression. The increased Piezo1-mediated calcium flow may play an important role in cytoskeleton reorganization since it induces actin stress fibers formation, a well-known characteristic of fibroblast transdifferentiation into the activated myofibroblast. Moreover, Piezo1 activity stimulates ECM and cytokines production, which in turn promotes the phenoconversion of adjacent fibroblasts into new myofibroblasts, enhancing the invasive character. Thus, by assuming the Piezo1 involvement in the activation of intrinsic fibroblasts, recruitment of new myofibroblasts, and uncontrolled excessive ECM production, a new approach to blocking the fibrotic progression can be predicted. Therefore, targeted therapies against Piezo1 could also be beneficial for cardiac fibrosis. |
first_indexed | 2024-03-09T05:24:45Z |
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id | doaj.art-d7f60b19bdca490ebf8db2d77a36890b |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T05:24:45Z |
publishDate | 2022-07-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-d7f60b19bdca490ebf8db2d77a36890b2023-12-03T12:38:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315806510.3390/ijms23158065Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic RemodelingNicoletta Braidotti0Suet Nee Chen1Carlin S. Long2Dan Cojoc3Orfeo Sbaizero4Department of Physics, University of Trieste, Via A. Valerio 2, 34127 Trieste, ItalyCU-Cardiovascular Institute, University of Colorado Anschutz Medical Campus, 12700 East 19th Ave., Aurora, CO 80045, USACenter for the Prevention of Heart and Vascular Disease, University of California, 555 Mission Bay Blvd South, Rm 352K, San Francisco, CA 94143, USAInstitute of Materials, National Research Council of Italy (CNR-IOM), Area Science Park Basovizza, Strada Statale 14, Km 163,5, 34149 Trieste, ItalyDepartment of Engineering and Architecture, University of Trieste, Via A. Valerio 6/A, 34127 Trieste, ItalyFibrotic tissues share many common features with neoplasms where there is an increased stiffness of the extracellular matrix (ECM). In this review, we present recent discoveries related to the role of the mechanosensitive ion channel Piezo1 in several diseases, especially in regulating tumor progression, and how this can be compared with cardiac mechanobiology. Based on recent findings, Piezo1 could be upregulated in cardiac fibroblasts as a consequence of the mechanical stress and pro-inflammatory stimuli that occurs after myocardial injury, and its increased activity could be responsible for a positive feedback loop that leads to fibrosis progression. The increased Piezo1-mediated calcium flow may play an important role in cytoskeleton reorganization since it induces actin stress fibers formation, a well-known characteristic of fibroblast transdifferentiation into the activated myofibroblast. Moreover, Piezo1 activity stimulates ECM and cytokines production, which in turn promotes the phenoconversion of adjacent fibroblasts into new myofibroblasts, enhancing the invasive character. Thus, by assuming the Piezo1 involvement in the activation of intrinsic fibroblasts, recruitment of new myofibroblasts, and uncontrolled excessive ECM production, a new approach to blocking the fibrotic progression can be predicted. Therefore, targeted therapies against Piezo1 could also be beneficial for cardiac fibrosis.https://www.mdpi.com/1422-0067/23/15/8065fibroblastsmyofibroblastsfibrosisheart diseasescardiomyopathiesfibroblasts activation |
spellingShingle | Nicoletta Braidotti Suet Nee Chen Carlin S. Long Dan Cojoc Orfeo Sbaizero Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling International Journal of Molecular Sciences fibroblasts myofibroblasts fibrosis heart diseases cardiomyopathies fibroblasts activation |
title | Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling |
title_full | Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling |
title_fullStr | Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling |
title_full_unstemmed | Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling |
title_short | Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling |
title_sort | piezo1 channel as a potential target for hindering cardiac fibrotic remodeling |
topic | fibroblasts myofibroblasts fibrosis heart diseases cardiomyopathies fibroblasts activation |
url | https://www.mdpi.com/1422-0067/23/15/8065 |
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