Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes

Vellino, Sanela; Oddou, Christiane; Rivier, Paul; Boyault, Cyril; Hiriart-Bryant, Edwige; Kraut, Alexandra; Martin, René; Couté, Yohann; Knölker, Hans‐Joachim; Valverde, Miguel A.; Albigès-Rizo, Corinne; Destaing, Olivier

doi:10.1083/jcb.201910079

Cited by 12 publications

(10 citation statements)

References 80 publications

(110 reference statements)

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“…We found that TRPV4‐mediated reduction of β 1 integrin expression in whole cell lysates or in plasma membrane fractions was consistent with the decreased β 1 integrin mRNA in TRPV4‐reconstituted cells. While some studies have suggested that TRPV4 influences β 1 integrin function at the plasma membrane, no insights have been provided that relate to potential regulatory mechanisms 44–46 . Our finding that TRPV4 expression was associated with a reduction in β 1 integrin transcript level indicates that this regulation occurs upstream of β 1 integrin protein expression.…”

Section: Discussionmentioning

confidence: 63%

TRPV4 regulates β1 integrin‐mediated cell–matrix adhesions and collagen remodeling

Wang

et al. 2023

The FASEB Journal

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Transient Receptor Potential Vanilloid-type 4 (TRPV4) is a mechanosensitive, Ca 2+ -permeable plasma membrane channel that associates with focal adhesions, influences collagen remodeling, and is associated with fibrotic processes through undefined mechanisms. While TRPV4 is known to be activated by mechanical forces transmitted through collagen adhesion receptors containing the β1 integrin, it is not understood whether TRPV4 affects matrix remodeling by altering β1 integrin expression and function. We tested the hypothesis that TRPV4 regulates collagen remodeling through its impact on the β1 integrin in cell-matrix adhesions. In cultured fibroblasts derived from mouse gingival connective tissues, which exhibit very rapid collagen turnover, we found that higher TRPV4 expression is associated with reduced β1 integrin abundance and adhesion to collagen, reduced focal adhesion size and total adhesion area, and reduced alignment and compaction of extracellular fibrillar collagen. The reduction of β1 integrin expression mediated by TRPV4 is associated with the upregulation of miRNAs that target β1 integrin mRNA. Our data suggest a novel mechanism by which TRPV4 modulates collagen remodeling through post-transcriptional downregulation of β1 integrin expression and function.

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Section: Discussionmentioning

confidence: 63%

TRPV4 regulates β1 integrin‐mediated cell–matrix adhesions and collagen remodeling

Wang

et al. 2023

The FASEB Journal

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“…TRPV4, as a mechanical sensor on the surface of cells, also plays a vital role in energy metabolism. Several previous studies have shown that ablation of TRPV4 inhibits ROS production in endothelial cells and immune cells by repairing the process of oxidative phosphorylation [ 58 , 59 ]. Our study supported their conclusion, LPS stimulation (M1 macrophages) resulted in a large elevation in mitochondrial reactive oxygen species (ROS) generation, whereas HC067047 treatment decreased the production of ROS.…”

Section: Discussionmentioning

confidence: 99%

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

Sun

et al. 2022

Antioxidants

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Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.

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“…Yet, the identification of the specific roles of ion channels at different steps of complex adhesive and degradative functions of invadosomes remains challenging. For example, it has been recently shown that TRPV4 calcium channel colocalizes with β1-integrins at the invadosome periphery and regulates the coupling of acto-adhesive and degradative functions(Vellino et al , 2021).…”

Section: Discussionmentioning

confidence: 99%

Expression of neuronal Na+ leak channel, NALCN, provides for persistent invasion of metastasizing cancer cells

Iamshanova

Gordienko

Folcher

et al. 2020

Preprint

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Cytosolic Ca2+ oscillations provide signaling input to several effector systems of the cell. These include neuronal development, migration and networking. Although similar signaling events are hijacked by highly aggressive cancer cells, the mechanism(s) driving the ′neuron-like′ remodeling of the intracellular ionic signature upon cancer progression remains largely elusive. Here, we identify the ′neuronal′ Na+ leak channel, NALCN, in metastatic cells at the hot spots of invadopodia formation and Ca2+ event initiation. Mechanistically, NALCN-mediated Na+ influx associates functionally with plasmalemmal and mitochondrial Na+/Ca2+ exchangers (NCX and NCLX), reactive oxygen species (ROS) and store-operated Ca2+ entry (SOCE)/endoplasmic reticulum Ca2+ uptake (SERCA) systems to generate intracellular Ca2+ oscillations. In turn, the oscillatory activity promotes Src-regulated actin remodeling, Ca2+-dependent secretion of proteolytic enzymes and leads to invadopodogenesis, resulting in tumor progression and metastatic lesions in vivo . Thus, we have uncovered malignant assignment of NALCN giving rise to a critical intracellular Na+/Ca2+ signaling axis.

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Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes

Cited by 12 publications

References 80 publications

TRPV4 regulates β1 integrin‐mediated cell–matrix adhesions and collagen remodeling

TRPV4 regulates β1 integrin‐mediated cell–matrix adhesions and collagen remodeling

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

Expression of neuronal Na+ leak channel, NALCN, provides for persistent invasion of metastasizing cancer cells

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