TRPV4—A Missing Link Between Mechanosensation and Immunity

Michalick, Laura; Kuebler, Wolfgang M.

doi:10.3389/fimmu.2020.00413

Cited by 85 publications

(88 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In regard to respiratory infections, recent studies report that TRPV4 inhibition may reduce bacterial clearance of Pseudomonas aeruginosa by macrophages (36). However, TRPV4 inhibition seems beneficial in lung infection with Streptococcus pneumoniae, the most frequent microbial cause of community-acquired pneumonia (29). Additionally, an earlier study documenting the role of TRPV4 in alveolar barrier integrity in vivo demonstrated that ventilator-induced lung injury depended on TRPV4 function in macrophages (19,20).…”

Section: Commentary and Caveatsmentioning

confidence: 99%

Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach

Kuebler

Jordt

Liedtke

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Commentary and Caveatsmentioning

confidence: 99%

Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach

Kuebler

Jordt

Liedtke

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mechanosensitive channel, TRPV4 has been implicated in mouse models of lung injury/fibrosis, which include hydrochloric acid, pulmonary edema, ventilator-associated lung parenchymal overdistension, and from our group, pulmonary fibrosis ( 50 – 53 ). The recent mini-review by Michalick and Kuebler in Frontiers Immunology further supports the concept that TRPV4 may connect mechanosensation to immunity in the lung ( 54 ). Given TRPV4's published role on regulating activity and infectivity of RNA viruses such as Zika, it remains possible that TRPV4 plays a role in the profound lung injury observed in the current SARS-CoV-2 pandemic ( 55 ).…”

Section: The Trpv4 Channel and Mechanobiology Of The Lungmentioning

confidence: 80%

The Role of TRPV4 in Regulating Innate Immune Cell Function in Lung Inflammation

et al. 2020

View full text Add to dashboard Cite

Ion channels/pumps are essential regulators of innate immune cell function. Macrophages have been increasingly recognized to have phenotypic plasticity and location-specific functions in the lung. Transient receptor potential vanilloid 4 (TRPV4) function in lung injury has been shown to be stimulus-and cell-type specific. In the current review, we discuss the importance of TRPV4 in macrophages and its role in phagocytosis and cytokine secretion in acute lung injury/acute respiratory distress syndrome (ARDS). Furthermore, TRPV4 controls a MAPK molecular switch from predominately c-Jun N-terminal kinase, JNK activation, to that of p38 activation, that mediates phagocytosis and cytokine secretion in a matrix stiffness-dependent manner. Expanding knowledge regarding the downstream mechanisms by which TRPV4 acts to tailor macrophage function in pulmonary inflammatory diseases will allow for formulation of novel therapeutics.

show abstract

“…The transient receptor potential vanilloid 4 (TRPV4) channel is a mechano-sensitive and immuno-sensitive calcium transport channel which functions to maintain pulmonary epithelial cell homeostasis. Increased TRPV4 channel activity has been implicated in ARDS pathology particularly in the context of lung stiffness [ 44 , 45 ], leading to alveolar epithelial and endothelial barrier dysfunction, activation of innate immune cells, and potentiation of pro-inflammatory cytokine release, oxidative stress, and extracellular matrix deposition [ 45 , 46 ]. TRPV4 −/− mice are protected against VILI [ 47 ] and chemically induced ALI [ 44 ], while TRPV4 channel inhibitors GSK2220691 and GSK2337429A also reduced ALI [ 44 ].…”

Section: Therapies In Clinical Trials For Ardsmentioning

confidence: 99%

Emerging pharmacological therapies for ARDS: COVID-19 and beyond

et al. 2020

View full text Add to dashboard Cite

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies ‘precision medicines.’ It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.

show abstract

TRPV4—A Missing Link Between Mechanosensation and Immunity

Cited by 85 publications

References 97 publications

Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach

Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach

The Role of TRPV4 in Regulating Innate Immune Cell Function in Lung Inflammation

Emerging pharmacological therapies for ARDS: COVID-19 and beyond

Contact Info

Product

Resources

About