TRPV4 is dispensable for the development of airway allergic asthma

Abstract

Allergic asthma is one of the most common immune-mediated disorders affecting the lungs. It is characterized clinically by airway hyperresponsiveness, eosinophilia, enhanced IL-4 and IL-13, peribronchial inflammation with mononuclear cell infiltration, and goblet cell hyperplasia associated with increased mucus production. However, chronic asthma with repeated exposures to inhaled allergens can result in subepithelial pulmonary fibrosis. The transient receptor potential cation channel subfamily V member 4 (TRPV4) protein can promote the generation of myofibroblasts and pulmonary fibrosis. Here, we investigated the possibility that TPRV4 facilitates the development of allergic asthma and subsequent pulmonary fibrosis in the lung. To test this, wild-type (WT) and TPRV4 gene knockout (KO) mice were repeatedly sensitized with chicken ovalbumin (OVA) and repeatedly subjected to aerosol challenge with 1% OVA. We found that there were no significant differences in the development of allergic asthma between the WT and TPRV4 KO mice. Both groups of mice exhibited similar levels of airway hyperresponsiveness, IL-13, IL-5, OVA-specific IgE, eosinophilia, mucus-secreting goblet cell hyperplasia, and deposition of collagen fiber, which is a hallmark of the pulmonary fibrosis. Thus, these data suggest that TPRV4 protein is dispensable in the initiation and development of airway asthma and subsequent fibrosis.

Ca2+ Signaling by TRPV4 Channels in Respiratory Function and Disease

“…Asthma is a chronic inflammatory disease of the upper airways induced by repeated exposure to specific allergens, which results in activation of epithelial cells and acute bronchoconstriction [77]. In a chicken ovalbumin (OVA) model of asthma, TRPV4-/-mice developed similar levels of airway hyper-responsiveness compared to wild-type (WT) mice [78], although TRPV4 protein levels were increased in WT animals [79]. TRPV4deficient mice were however protected from airway remodeling in a house dust mite (HDM) model, which is more relevant to the human situation [80].…”

The Emerging Role of Ion Channels in the Pathophysiology and Treatments of Asthma

“…Other TRPV channels such as TRPV4 channels may be dispensable for the development of allergic asthma [56]. TRPV4 knockout and wild-type mice sensitized and challenged by OVA express similar levels of allergenspecific IgE, Th2 cytokines, and eosinophils [56].…”

“…Other TRPV channels such as TRPV4 channels may be dispensable for the development of allergic asthma [56]. TRPV4 knockout and wild-type mice sensitized and challenged by OVA express similar levels of allergenspecific IgE, Th2 cytokines, and eosinophils [56]. Although TRPV4 knockout mice have slightly higher AHR in response to increasing doses of β-methacholine than wild-type mice, there are no significant differences in airway resistance between these groups [56].…”

Emerging roles of the TRPV4 channel in bladder physiology and dysfunction

“…arachidonic acid metabolites such as 5,6-epoxyeicosatrienoic acid) stimuli (Garcia-Elias et al 2014). Distribution of TRPV4 in various tissues, such as airway (Palaniyandi et al 2020), heart (Adapala et al 2020), skin (Szabo et al 2019), intestine (Huang et al 2018), brain (Shibasaki et al 2020) and the urinary bladder, has been reported. With significant changes in bladder functions noted in TRPV4 deficient mice (Gevaert et al 2007), there has been a growing interest in TRPV4 as a therapeutic target for bladder dysfunctions.…”

“…Distribution of TRPV4 in various tissues, such as airway (Palaniyandi et al . 2020), heart (Adapala et al . 2020), skin (Szabo et al .…”