Related Experiment Video
Updated: Sep 3, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling
Nicoletta Braidotti1,2, Suet Nee Chen3, Carlin S Long4
1Department of Physics, University of Trieste, Via A. Valerio 2, 34127 Trieste, Italy.
Abstract:
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.
Insights
The mechanosensitive ion channel Piezo1, when upregulated after heart injury, drives cardiac fibrosis by promoting fibroblast activation and extracellular matrix production. Targeting Piezo1 may offer a novel therapeutic strategy for fibrotic diseases.
Area of Science:
- Cardiovascular mechanobiology
- Cellular mechanotransduction
- Fibrosis research
Background:
- Fibrotic tissues and neoplasms exhibit increased extracellular matrix (ECM) stiffness.
- Mechanosensitive ion channels, like Piezo1, play roles in disease progression.
- Cardiac fibrosis involves fibroblast activation and excessive ECM deposition.
Purpose of the Study:
- To review the role of Piezo1 in disease, focusing on tumor progression and cardiac mechanobiology.
- To explore Piezo1's involvement in cardiac fibrosis following myocardial injury.
- To identify Piezo1 as a potential therapeutic target for fibrotic conditions.
Main Methods:
- Review of recent scientific literature on Piezo1.
- Analysis of Piezo1's role in fibroblast activation and ECM production.
- Comparison of Piezo1's function in cardiac mechanobiology and cancer.
Main Results:
- Piezo1 is upregulated in cardiac fibroblasts due to mechanical stress and inflammation post-myocardial injury.
- Increased Piezo1 activity drives a positive feedback loop, exacerbating cardiac fibrosis.
- Piezo1 mediates calcium influx, promoting cytoskeleton remodeling and myofibroblast differentiation.
Conclusions:
- Piezo1 activation contributes to fibroblast activation, myofibroblast recruitment, and excessive ECM production in cardiac fibrosis.
- Targeting Piezo1 presents a potential therapeutic avenue for mitigating fibrotic progression.
- Understanding Piezo1's role offers new insights into treating fibrotic diseases, including cardiac fibrosis.
Related Concept Videos
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:12Mechanically-gated Ion Channels