Pathophysiological Roles of the TRPV4 Channel in the Heart

Chaigne, Sébastien; Barbeau, Solène; Ducret, Thomas; Guinamard, Romain; Benoist, David

doi:10.3390/cells12121654

Cited by 9 publications

(4 citation statements)

References 183 publications

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“…Due to the two negatively charged aspartate residues within the conserved lower gate, it is easier for divalent ions than monovalent ions to pass through TRPV4. As a result, TRPV4 is mainly permeable to Ca 2+ rather than other ions, with the following permeability sequence: Ca 2+ >> Mg 2+ > K + > Na + , whereby the permeability for Ca 2+ is about five times higher than that of Mg 2+ , and about ten times higher than for Na + [46,47]. Four identical TRPV4 monomers form a functional channel.…”

Section: Protein and Channel Structure Of Trpv4mentioning

confidence: 99%

“…TRPV4 mechanosensor is an integral factor in the progression of tissue repair and fibrotic disorders across different organs, including the skin, lungs, liver, kidneys, brain, blood vessels and heart [47]. In this section, we provide a comprehensive summary of the current understanding regarding the functions of TRPV4-induced Ca 2+ oscillation in each specific organ (Figure 4).…”

Section: Function Of Trpv4-evoked Ca 2+ Oscillations In Injury Repair...mentioning

confidence: 99%

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The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

Jiang,

Guo,

Dai

et al. 2024

IJMS

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The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such as mechanical stress, osmotic pressure, and temperature. TRPV4 enables the entry of cation ions, particularly calcium ions, into the cell. Activation of TRPV4 channels initiates calcium oscillations, which trigger intracellular signaling pathways involved in a plethora of cellular processes, including tissue repair. Widely expressed throughout the body, TRPV4 can be activated by a wide array of physicochemical stimuli, thus contributing to sensory and physiological functions in multiple organs. This review focuses on how TRPV4 senses environmental cues and thereby initiates and maintains calcium oscillations, critical for responses to organ injury, tissue repair, and fibrosis. We provide a summary of TRPV4-induced calcium oscillations in distinct organ systems, along with the upstream and downstream signaling pathways involved. In addition, we delineate current animal and disease models supporting TRPV4 research and shed light on potential therapeutic targets for modulating TRPV4-induced calcium oscillation to promote tissue repair while reducing tissue fibrosis.

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Section: Protein and Channel Structure Of Trpv4mentioning

confidence: 99%

Section: Function Of Trpv4-evoked Ca 2+ Oscillations In Injury Repair...mentioning

confidence: 99%

The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

Jiang,

Guo,

Dai

et al. 2024

IJMS

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“…DADLE could enhance the OGD/R-damaged cellular viability, elevate the mitochondrial membrane potential and promote ATP synthesis It has been reported that TRPV4 is expressed in endothelial cells and modulates mitochondrial activity. 17 DADLE offers neuroprotection against acute mitochondrial dysfunction. 18 Therefore, we hypothesise that the protective effect of DADLE on BMECs might be related to mitochondria.…”

Section: Open Accessmentioning

confidence: 99%

Delta opioid peptide [D-ala2, D-leu5]-Enkephalin’s ability to enhance mitophagy via TRPV4 to relieve ischemia/reperfusion injury in brain microvascular endothelial cells

Deng,

Chen,

Zhang

et al. 2024

Stroke Vasc Neurol

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BackgroundLocal brain tissue can suffer from ischaemia/reperfusion (I/R) injury, which lead to vascular endothelial damage. The peptide δ opioid receptor (δOR) agonist [D-ala2, D-leu5]-Enkephalin (DADLE) can reduce apoptosis caused by acute I/R injury in brain microvascular endothelial cells (BMECs).ObjectiveThis study aims to explore the mechanism by which DADLE enhances the level of mitophagy in BMECs by upregulating the expression of transient receptor potential vanilloid subtype 4 (TRPV4).MethodsBMECs were extracted and made to undergo oxygen-glucose deprivation/reoxygenation (OGD/R) accompanied by DADLE. RNA-seq analysis revealed that DADLE induced increased TRPV4 expression. The CCK-8 method was used to assess the cellular viability; quantitative PCR (qPCR) was used to determine the mRNA expression ofDrp1; western blot was used to determine the expression of TRPV4 and autophagy-related proteins; and calcium imaging was used to detect the calcium influx. Autophagosomes in in the cells’ mitochondria were observed by using transmission electron microscopy. ELISA was used to measure ATP content, and a JC-1 fluorescent probe was used to detect mitochondrial membrane potential.ResultsWhen compared with the OGD/R group, OGD/R+DADLE group showed significantly enhanced cellular viability; increased expression of TRPV4, Beclin-1, LC3-II/I, PINK1 and Parkin; decreased p62 expression; a marked rise in calcium influx; further increases in mitophagy, an increase in ATP synthesis and an elevation of mitochondrial membrane potential. These protective effects of DADLE can be blocked by a TRPV4 inhibitor HC067047 or RNAi of TRPV4.ConclusionDADLE can promote mitophagy in BMECs through TRPV4, improving mitochondrial function and relieving I/R injury.

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“…Transient receptor potential vanilloid 4 is a nonselective Ca 2+ -permeable cation channel that belongs to the transient receptor potential (TRP) subfamily [1,2]. The TRPV4 channel exhibits membranous expression and can be found in the brain, eyes, urinary system, gastrointestinal tract, skin, epithelial, vasculature, several musculoskeletal tissues, and innate immune system cells [2,3]. The TRPV4 ion channel activity is affected by changes in the cell membrane following heat, swelling, pH, mechanical, and biological stimuli [1,4].…”

Section: Introductionmentioning

confidence: 99%

Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog

Babaniamansour,

Jacho,

Niedzielski

et al. 2024

Biomedicines

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Investigating macrophage plasticity emerges as a promising strategy for promoting tissue regeneration and can be exploited by regulating the transient receptor potential vanilloid 4 (TRPV4) channel. The TRPV4 channel responds to various stimuli including mechanical, chemical, and selective pharmacological compounds. It is well documented that treating cells such as epithelial cells and fibroblasts with a TRPV4 agonist enhances the Ca2+ influx to the cells, which leads to secretion of pro-inflammatory cytokines, while a TRPV4 antagonist reduces both Ca2+ influx and pro-inflammatory cytokine secretion. In this work, we investigated the effect of selective TRPV4 modulator compounds on U937-differentiated macrophages encapsulated within three-dimensional (3D) matrices. Despite offering a more physiologically relevant model than 2D cultures, pharmacological treatment of macrophages within 3D collagen matrices is largely overlooked in the literature. In this study, pro-inflammatory macrophages were treated with an agonist, 500 nM of GSK1016790A (TRPV4(+)), and an antagonist, 10 mM of RN-1734 (TRPV4(−)), to elucidate the modulation of the TRPV4 channel at both cellular and extracellular levels. To evaluate macrophage phenotypic alterations within 3D collagen matrices following TRPV4 modulator treatment, we employed structural techniques (SEM, Masson’s trichrome, and collagen hybridizing peptide (CHP) staining), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Our data reveal that pharmacological modulation of the macrophage TRPV4 channel alters the cytoskeletal structure of macrophages and influences the 3D structure encapsulating them. Moreover, we proved that treating macrophages with a TRPV4 agonist and antagonist enhances the expression of pro- and anti-inflammatory genes, respectively, leading to the upregulation of surface markers CD80 and CD206. In the TRPV4(−) group, the CD206 gene and CD206 surface marker were significantly upregulated by 9- and 2.5-fold, respectively, compared to the control group. These findings demonstrate that TRPV4 modulation can be utilized to shift macrophage phenotype within the 3D matrix toward a desired state. This is an innovative approach to addressing inflammation in musculoskeletal tissues.

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Pathophysiological Roles of the TRPV4 Channel in the Heart

Cited by 9 publications

References 183 publications

The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

Delta opioid peptide [D-ala2, D-leu5]-Enkephalin’s ability to enhance mitophagy via TRPV4 to relieve ischemia/reperfusion injury in brain microvascular endothelial cells

Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog

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