ArticleScience signaling2021
Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- Reprogramming macrophage mechanosensation via TRPV4 modulating mechano-immunotherapy controls fibrotic encapsulation of biomaterial implants.Bioactive materials · 2026Article
- TRPV4 mediates macrophage polarization involved in inflammatory root resorption induced by mechanical pressure.Channels (Austin, Tex.) · 2026Article
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- A novel role for TRPV1 in macrophage giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- A novel endosome-escaping, macrophage-targeted nanoparticle platform for miR-146a delivery with favorable in vivo biodistribution and biocompatibility.bioRxiv : the preprint server for biology · 2026Article
- Endosome-escaping engineered LNP-miR146a with in vivo biodistribution to mitigate inflammation and foreign body giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- Co-culture with fibroblasts in stiff 3D scaffolds increases CD54 and CD140a expression on macrophages.Frontiers in immunology · 2026Article
- A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation.Advanced healthcare materials · 2026Article
- Piezo1 as a mechanical checkpoint in T cell immunotherapy for solid tumors.Frontiers in pharmacology · 2026Review
- Diminished fibrotic encapsulation and comparable physicochemical properties of poly (styrene-Frontiers in bioengineering and biotechnology · 2026Article
- Targeting delayed healing tissues: immune reprogramming of adaptive immune cells by biomaterials.Regenerative biomaterials · 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
- TRP Channels from Sensory Coding to Physiology.Metabolites · 2025Review
- How do mechanical forces impact macrophages in the processes of mechanosensing and mechanotransduction?Journal of Zhejiang University. Science. B · 2025Review
- 3D In Vitro Models of Breast Cancer: Current Challenges and Future Prospects Toward Recapitulating the Microenvironment and Mimicking Key Processes.Advanced biology · 2025Review
- The foreign body response to biomaterial implants is reduced by co-inhibition of TLR2 and TLR4.Acta biomaterialia · 2025Article
- TRPV4 Channel Contributes to Aortic Root Stiffening and Atherosclerotic Lesion Development.Arteriosclerosis, thrombosis, and vascular 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
- Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants.Biomaterials · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Implantation of biomaterials or devices into soft tissue often leads to the development of the foreign body response (FBR), an inflammatory condition that can cause implant failure, tissue injury, and death of the patient. Macrophages accumulate and fuse to generate destructive foreign body giant cells (FBGCs) at the tissue-implant interface, leading to the development of fibrous scar tissue around the implant that is generated by myofibroblasts. We previously showed that the FBR in vivo and FBGC formation in vitro require transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel. Here, we report that TRPV4 was required specifically for the FBR induced by implant stiffness independently of biochemical cues and for intracellular stiffening that promotes FBGC formation in vitro. TRPV4 deficiency reduced collagen deposition and the accumulation of macrophages, FBGCs, and myofibroblasts at stiff, but not soft, implants in vivo and inhibited macrophage-induced differentiation of wild-type fibroblasts into myofibroblasts in vitro. Atomic force microscopy demonstrated that TRPV4 was required for implant-adjacent tissue stiffening in vivo and for cytoskeletal remodeling and intracellular stiffening induced by fusogenic cytokines in vitro. Together, these data suggest a mechanism whereby a reciprocal functional interaction between TRPV4 and substrate stiffness leads to cytoskeletal remodeling and cellular force generation to promote FBGC formation during the FBR.
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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.