ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
Hydrogel cultures reveal Transient Receptor Potential Vanilloid 4 regulation of myofibroblast activation and proliferation in valvular interstitial cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- From biomechanical mechanisms to clinical reasoning: Deciphering mechanobiological drivers of aortic valve calcification for precision therapy.Mechanobiology in medicine · 2026Review
- Decoupling Mechanical Confinement and Fibrotic Extracellular Matrix Signaling in Vestibular Schwannoma Using Tunable 3D Hydrogels.Cellular and molecular bioengineering · 2026Article
- Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.Materials today. Bio · 2026Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- TRPV4-Mediated Mechanosensing Regulates the Endothelial-to-Mesenchymal Transition: Implications for Atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- PTEN Regulates Myofibroblast Activation in Valvular Interstitial Cells Based on Subcellular Localization.Advanced biology · 2025Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- Contribution of the TRPM4 Channel to Osteogenic Differentiation of Human Aortic Valve Interstitial Cells.Journal of the American Heart Association · 2025Article
- Hydrogel Elastic Energy: A Stressor Triggering an Adaptive Stress-Mediated Cell Response.Advanced healthcare materials · 2025Article
- Piezo1 and tissue fibrosis: insights into its role and potential for modulation.Burns & trauma · 2025Review
- Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination.Nature communications · 2024Article
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
- Cell-extracellular matrix mechanotransduction in 3D.Nature reviews. Molecular cell biology · 2023Review
- Ion Channels in the Development and Remodeling of the Aortic Valve.International journal of molecular sciences · 2023Review
- Engineered hydrogels for mechanobiology.Nature reviews. Methods primers · 2022Article
- Chemical and molecular tools to probe biological sex differences at multiple length scales.Journal of materials chemistry. B · 2022Review
- Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
As aortic valve stenosis develops, valve tissue becomes stiffer. In response to this change in environmental mechanical stiffness, valvular interstitial cells (VICs) activate into myofibroblasts. We aimed to investigate the role of mechanosensitive calcium channel Transient Receptor Potential Vanilloid type 4 (TRPV4) in stiffness induced myofibroblast activation. We verified TRPV4 functionality in VICs using live calcium imaging during application of small molecule modulators of TRPV4 activity. We designed hydrogel biomaterials that mimic mechanical features of healthy or diseased valve tissue microenvironments, respectively, to investigate the role of TRPV4 in myofibroblast activation and proliferation. Our results show that TRPV4 regulates VIC proliferation in a microenvironment stiffness-independent manner. While there was a trend toward inhibiting myofibroblast activation on soft microenvironments during TRPV4 inhibition, we observed near complete deactivation of myofibroblasts on stiff microenvironments. We further identified Yes-activated protein (YAP) as a downstream target for TRPV4 activity on stiff microenvironments. Mechanosensitive TRPV4 channels regulate VIC myofibroblast activation, whereas proliferation regulation is independent of the microenvironmental stiffness. Collectively, the data suggests differential regulation of stiffness-induced proliferation and myofibroblast activation. Our data further suggest a regulatory role for TRPV4 regarding YAP nuclear localization. TRPV4 is an important regulator for VIC myofibroblast activation, which is linked to the initiation of valve fibrosis. Although more validation studies are necessary, we suggest TRPV4 as a promising pharmaceutical target to slow aortic valve stenosis progression.
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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.