Ca2+ Signaling by TRPV4 Channels in Respiratory Function and Disease

Rajan, Suhasini; Schremmer, Christian; Weber, Jonas; Alt, Philipp; Geiger, Fabienne; Dietrich, Alexander

doi:10.3390/cells10040822

Cited by 18 publications

(11 citation statements)

References 117 publications

(142 reference statements)

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“…TRPV4 cation channels elicit focal Ca 2+ influx events at the plasma membrane (Ca 2+ sparklets), allowing for localized signal targeting and providing a trigger for larger Ca 2+ -induced Ca 2+ release events (i.e., from the endoplasmic reticulum) ( Sullivan et al, 2012 ; Lin et al, 2015 ; Heathcote et al, 2019 ; McFarland et al, 2020 ). Growing evidence supports involvement of these channels in shear stress and agonist-mediated endothelial signaling, and changes in TRPV4 signaling are linked to disease states including hypertension, diabetes and pulmonary edema ( Hartmannsgruber et al, 2007 ; Mendoza et al, 2010 ; Sonkusare et al, 2012 ; Ma et al, 2013 ; Monaghan et al, 2015 ; Zhang et al, 2018 ; Daneva et al, 2021 ; Rajan et al, 2021 ). In the current study, we observed TRPV4 channels expressed in the intima as well as the media of peripheral arteries, and even within neointima of arteries from CVD patients.…”

Section: Discussionmentioning

confidence: 99%

Restricted Intimal Ca2+ Signaling Associated With Cardiovascular Disease

Taylor

Lowery

et al. 2022

Front. Physiol.

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Endothelial dysfunction is a key feature of cardiovascular disease (CVD) including atherosclerosis. Impaired endothelial signaling leads to plaque formation, vascular wall remodeling and widespread cardiovascular dysregulation. The specific changes along the vascular intima associated with atherosclerosis, including the vulnerable circulation downstream of the flow obstruction, remain poorly understood. Previous findings from animal models suggest that preservation of a distinct Ca2+ signaling profile along the arterial endothelial network is crucial for maintaining vasculature homeostasis and preventing arterial disease. Ca2+ signaling in the intact human artery intima has not been well characterized. Here, we employed confocal imaging and a custom analysis algorithm to assess the spatially and temporally dynamic Ca2+ signaling profiles of human peripheral arteries isolated from the amputated legs of patients with advanced CVD (peripheral artery disease and/or diabetes) or patients who had lost limbs due to non-cardiovascular trauma. In all tibial artery branches (0.5–5 mm diameter) assessed, the intima consistently elicited a broad range of basal Ca2+ signals ranging from isolated focal transients to broad waves. Arteries from patients with existing CVD displayed a restricted intimal Ca2+ signaling pattern characterized by diminished event amplitude and area. Stimulation of type-4 vanilloid transient receptor potential channels (TRPV4) amplified endothelial Ca2+ signals; however, these signals remained smaller and spatially confined in arteries from patients with CVD verses those without CVD. Our findings reveal a characteristic underlying basal Ca2+ signaling pattern within the intima of human peripheral arteries and suggest a distinct truncation of the inherent Ca2+ profile with CVD.

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Section: Discussionmentioning

confidence: 99%

Restricted Intimal Ca2+ Signaling Associated With Cardiovascular Disease

Taylor

Lowery

et al. 2022

Front. Physiol.

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“…We were able to show the expression of TRPV4 in both AT1 and AT2 cells and identified emphysema-like changes in the lungs of older TRPV4−/− mice, which favor ischemia-reperfusion(I/R)-induced edema formation, a serious drawback in lung transplantation ([ 119 ] reviewed in [ 8 ]). AT2 cells are also able to replace AT1 cells, a capacity that was, however, not dependent on TRPV4 channels [ 119 ].…”

Section: Trp Expression and Function In Alveolimentioning

confidence: 99%

“…This review will summarize TRP functions in the airways, their roles in diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema. Our manuscript also serves as an update of recent reviews by us [ 5 , 6 , 7 , 8 ] and will focus on non-neuronal tissues and extensively studied TRP members, such as TRPA1, TRPC6, TRPM2, TRPM5, TRPV2 and TRPV4.…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Müller¹,

Alt²,

Rajan³

et al. 2022

Cells

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Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed.

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“…While force-sensing occurs in or on the plasma membrane, forces can reach deep in the cell interior and to the nucleus [ 80 , 81 , 82 ]. Specific mechano-transducing elements on the cell surface, including cell adhesion protein complexes, primary cilia, G protein-coupled receptors, and mechanically gated ion channels [ 29 , 83 , 84 , 85 , 86 ], have been identified in lung cells, and progress has been achieved in deciphering signaling pathways that ultimately result in physiological or pathophysiological cellular responses [ 87 , 88 ]. Part of this progress has been achieved through the development of accurate technologies for the precise application and investigation of the complex intracellular, intercellular, and cell-matrix forces affecting lung development, function, and pathophysiological processes.…”

Section: Forces On Lung Cells and Tissuementioning

confidence: 99%

In Vitro Measurements of Cellular Forces and their Importance in the Lung—From the Sub- to the Multicellular Scale

Kolb

Schundner

Frick

et al. 2021

Life

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Throughout life, the body is subjected to various mechanical forces on the organ, tissue, and cellular level. Mechanical stimuli are essential for organ development and function. One organ whose function depends on the tightly connected interplay between mechanical cell properties, biochemical signaling, and external forces is the lung. However, altered mechanical properties or excessive mechanical forces can also drive the onset and progression of severe pulmonary diseases. Characterizing the mechanical properties and forces that affect cell and tissue function is therefore necessary for understanding physiological and pathophysiological mechanisms. In recent years, multiple methods have been developed for cellular force measurements at multiple length scales, from subcellular forces to measuring the collective behavior of heterogeneous cellular networks. In this short review, we give a brief overview of the mechanical forces at play on the cellular level in the lung. We then focus on the technological aspects of measuring cellular forces at many length scales. We describe tools with a subcellular resolution and elaborate measurement techniques for collective multicellular units. Many of the technologies described are by no means restricted to lung research and have already been applied successfully to cells from various other tissues. However, integrating the knowledge gained from these multi-scale measurements in a unifying framework is still a major future challenge.

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Ca2+ Signaling by TRPV4 Channels in Respiratory Function and Disease

Cited by 18 publications

References 117 publications

Restricted Intimal Ca2+ Signaling Associated With Cardiovascular Disease

Restricted Intimal Ca2+ Signaling Associated With Cardiovascular Disease

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

In Vitro Measurements of Cellular Forces and their Importance in the Lung—From the Sub- to the Multicellular Scale

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