ArticleJournal of molecular and cellular cardiology2013
TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 207 citations in OpenAlex.
- Nanomolar vanillin, an e-cigarette flavorant, appears to disrupt pluripotency and promote endodermal differentiation in human embryonic stem cells via TRPV4 activation.Human reproduction (Oxford, England) · 2026Article
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- Beyond the Brain: GABAergic Signaling as a Peripheral Modulator of Skin Barrier Immunity.International journal of molecular sciences · 2026Review
- Cardiac fibroblasts in myocardial injury and heart failure.European heart journal · 2026Review
- Shear Stress as a Driver of Retinal Müller Glia Survival and Fibrotic Reprogramming.Cell biochemistry and function · 2026Article
- Calcium Signaling in Cardiac Fibroblasts: Roles in Fibrosis and Therapeutic Implications.Cardiovascular drugs and therapy · 2026Review
- Advances in targeting myocardial fibrosis: integrating mechanisms and therapeutics.Frontiers in cardiovascular medicine · 2026Review
- The Potential Connection Between Mechanical Stress and Heart Failure with Preserved Ejection Fraction: Mechanistic Insights and Therapeutic Potential.International journal of medical sciences · 2026Review
- Integrative transcriptomic analysis revealed the roles and prognostic value of ion channels in hypertrophic cardiomyopathy.Frontiers in pharmacology · 2026Article
- TFAP4 exacerbates pathological cardiac fibrosis by modulating mechanotransduction.Cell insight · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Computational modelling of cardiac fibroblast signalling reveals a key role for CaThe Journal of physiology · 2025Article
- CaBiomedicines · 2025Review
- The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling.Channels (Austin, Tex.) · 2024Review
- Dynamic Changes in Ion Channels during Myocardial Infarction and Therapeutic Challenges.International journal of molecular sciences · 2024Review
- Cardiac Fibroblastic Niches in Homeostasis and Inflammation.Circulation research · 2024Review
- Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium.Scientific reports · 2024Article
- Wound Repair and CaCells · 2024Review
- TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6.International journal of molecular sciences · 2024Article
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The phenotypic switch underlying the differentiation of cardiac fibroblasts into hypersecretory myofibroblasts is critical for cardiac remodeling following myocardial infarction. Myofibroblasts facilitate wound repair in the myocardium by secreting and organizing extracellular matrix (ECM) during the wound healing process. However, the molecular mechanisms involved in myofibroblast differentiation are not well known. TGF-β has been shown to promote differentiation and this, combined with the robust mechanical environment in the heart, lead us to hypothesize that the mechanotransduction and TGF-β signaling pathways play active roles in the differentiation of cardiac fibroblasts to myofibroblasts. Here, we show that the mechanosensitve ion channel TRPV4 is required for TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts. We found that the TRPV4-specific antagonist AB159908 and siRNA knockdown of TRPV4 significantly inhibited TGFβ1-induced differentiation as measured by incorporation of α-SMA into stress fibers. Further, we found that TGF-β1-induced myofibroblast differentiation was dependent on ECM stiffness, a response that was attenuated by TRPV4 blockade. Finally, TGF-β1 treated fibroblasts exhibited enhanced TRPV4 expression and TRPV4-mediated calcium influx compared to untreated controls. Taken together these results suggest for the first time that the mechanosensitive ion channel, TRPV4, regulates cardiac fibroblast differentiation to myofibroblasts by integrating signals from TGF-β1 and mechanical factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.