A novel role for TRPV1 in macrophage giant cell formation
- 1University of Maryland, Department of Nutrition and Food Science, College Park, MD 20742
Abstract
TRPV1 (transient receptor potential vanilloid 1) is a non-selective cation channel with high permeability to Ca 2+ and is best known for its roles in sensory signaling. However, its function in immune cell biology, particularly in macrophage fusion, remains unknown. Cell fusion is a critical process in both physiological and pathological contexts, including development, tissue remodeling, and the foreign body response (FBR) to implanted biomaterials. During FBR, macrophages undergo fusion to form multinucleated foreign body giant cells (FBGCs), which contribute to implant degradation and fibrotic encapsulation. Here, we identify TRPV1 as a key regulator of macrophage multinucleation and FBGC formation. We demonstrate that TRPV1 is endogenously expressed in bone marrow-derived macrophages (BMDMs) and is upregulated in response to fusogenic cytokines and inflammatory stimuli. Functionally, TRPV1 promotes matrix stiffness-dependent macrophage adhesion and spreading, indicating a role in mechanosensitive signaling. We show that TRPV1 is required for efficient macrophage fusion under both cytokine-driven and matrix stiffness-mediated conditions. Mechanistically, TRPV1 links extracellular mechanical cues and cytokine signaling to cytoskeletal remodeling, facilitating the actin reorganization necessary for cell fusion. Importantly, TRPV1 deficiency does not alter TRPV4-mediated Ca 2+ signaling, demonstrating that TRPV1 operates independently of TRPV4, a known mechanosensitive channel implicated in FBR and FBGC formation. Collectively, these findings suggest TRPV1 as a previously unrecognized mechanosensitive regulator of macrophage fusion and FBGC formation. This work provides new insight into the molecular mechanisms governing FBR and identifies TRPV1 as a potential therapeutic target for improving biomaterial biocompatibility and mitigating fibrosis.
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BibTeX
@article{sankaran2026novel,
title = {{A novel role for TRPV1 in macrophage giant cell formation}},
author = {Karunakaran R. Sankaran and Mohammad I. Khan and Shaik O. Rahaman},
journal = {American journal of physiology. Cell physiology},
year = {2026},
month = aug,
doi = {10.1152/ajpcell.90011.2026},
url = {https://doi.org/10.1152/ajpcell.90011.2026},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A novel role for TRPV1 in macrophage giant cell formation
AU - Karunakaran R. Sankaran
AU - Mohammad I. Khan
AU - Shaik O. Rahaman
PY - 2026
DA - 2026/08/25
JO - American journal of physiology. Cell physiology
DO - 10.1152/ajpcell.90011.2026
UR - https://doi.org/10.1152/ajpcell.90011.2026
AB - TRPV1 (transient receptor potential vanilloid 1) is a non-selective cation channel with high permeability to Ca 2+ and is best known for its roles in sensory signaling. However, its function in immune cell biology, particularly in macrophage fusion, remains unknown. Cell fusion is a critical process in both physiological and pathological contexts, including development, tissue remodeling, and the foreign body response (FBR) to implanted biomaterials. During FBR, macrophages undergo fusion to form multinucleated foreign body giant cells (FBGCs), which contribute to implant degradation and fibrotic encapsulation. Here, we identify TRPV1 as a key regulator of macrophage multinucleation and FBGC formation. We demonstrate that TRPV1 is endogenously expressed in bone marrow-derived macrophages (BMDMs) and is upregulated in response to fusogenic cytokines and inflammatory stimuli. Functionally, TRPV1 promotes matrix stiffness-dependent macrophage adhesion and spreading, indicating a role in mechanosensitive signaling. We show that TRPV1 is required for efficient macrophage fusion under both cytokine-driven and matrix stiffness-mediated conditions. Mechanistically, TRPV1 links extracellular mechanical cues and cytokine signaling to cytoskeletal remodeling, facilitating the actin reorganization necessary for cell fusion. Importantly, TRPV1 deficiency does not alter TRPV4-mediated Ca 2+ signaling, demonstrating that TRPV1 operates independently of TRPV4, a known mechanosensitive channel implicated in FBR and FBGC formation. Collectively, these findings suggest TRPV1 as a previously unrecognized mechanosensitive regulator of macrophage fusion and FBGC formation. This work provides new insight into the molecular mechanisms governing FBR and identifies TRPV1 as a potential therapeutic target for improving biomaterial biocompatibility and mitigating fibrosis.
SN - 0363-6143
SN - 1522-1563
ER -