Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa

Ihara, Takeshi; Mitsui, Takahiko; Nakamura, Yuki; Kira, Satoru; Nakagomi, Hiroshi; Sawada, Norifumi; Hirayama, Yuri; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Youichi; Yoshiyama, Mitsuharu; Andersson, Karl‐Erik; Nakao, Akihiro; Takeda, Masayuki; Koizumi, Schuichi

doi:10.1371/journal.pone.0168234

Cited by 36 publications

(71 citation statements)

References 40 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Co-operation of vesicular ATP release and channel-mediated ATP release at the plasma membrane are frequently observed in the initiation of purinergic chemical transmission, which has been discussed elsewhere [7]. Very recently, Koizumi and his colleagues reported that clock genes regulate the expression of TRP4, connexin26, and VNUT in mouse bladder mucosa, indicating that ATP release is regulated under circadian rhythm [126].…”

Section: Urinary Bladdermentioning

confidence: 93%

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Moriyama

Hiasa

Sakamoto³

et al. 2017

Purinergic Signalling

View full text Add to dashboard Cite

Vesicular storage of ATP is one of the processes initiating purinergic chemical transmission. Although an active transport mechanism was postulated to be involved in the processes, a transporter(s) responsible for the vesicular storage of ATP remained unidentified for some time. In 2008, SLC17A9, the last identified member of the solute carrier 17 type I inorganic phosphate transporter family, was found to encode the vesicular nucleotide transporter (VNUT) that is responsible for the vesicular storage of ATP. VNUT transports various nucleotides in a membrane potential-dependent fashion and is expressed in the various ATP-secreting cells. Mice with knockout of the VNUT gene lose vesicular storage and release of ATP from neurons and neuroendocrine cells, resulting in blockage of the initiation of purinergic chemical transmission. Thus, VNUT plays an essential role in the vesicular storage and release of ATP. The VNUT knockout mice exhibit resistance for neuropathic pain and a therapeutic effect against diabetes by way of increased insulin sensitivity. Thus, VNUT inhibitors and suppression of VNUT gene expression may be used for therapeutic purposes through suppression of purinergic chemical transmission. This review summarizes the studies to date on VNUT and discusses what we have learned about the relevance of vesicular ATP release as a potential drug target.

show abstract

Section: Urinary Bladdermentioning

confidence: 93%

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Moriyama

Hiasa

Sakamoto³

et al. 2017

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…The time of the first sample collection was defined as 0 h (12 h after HSS). For the time course in vitro, the corresponding to the light period was set from 0 to 12 h, and the corresponding to the dark period was set from 12 to 20 h, according to the circadian gene expression pattern of mechano‐sensors and ARMM in the ex vivo mouse bladder mucosa in order to provide an easy understanding of diurnal gene expression pattern, in which the peak time was observed at zeitgeber time 12 …”

Section: Methodsmentioning

confidence: 99%

“…QRT‐PCR assays were performed as reported previously . The primer sequences are shown in Supporting information S1.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were diluted to the reference concentration, which represented the lowest concentration from the 0–20 h samples. Diluted lysates were then subjected to SDS‐PAGE using previously described methods . The transferred membrane was cut into several strips according to the product size of target protein.…”

Section: Methodsmentioning

confidence: 99%

“…In the lower urinary tract, we previously reported that Clock mutant mice show a nocturia (NOC) phenotype, which indicated that lower urinary tract function was also regulated by clock genes and that abnormalities in clock genes may induce NOC . Moreover, using the ex vivo mouse bladder mucosa, we revealed that clock genes regulate the transcription of mechano‐sensors such as transient receptor potential cation channel subfamily V member 4 ( TRPV4) and Piezo1 , and ATP release mediated molecules (ARMM) such as vesicular nucleotide transporter ( VNUT) and Connexin26 ( Cx26 ), which sense the bladder wall extension and send the signals for urination to the CNS via direct Clock protein binding to the promoter lesion on these genes . Thus, the circadian rhythm of the sensation of bladder fullness might be created by the circadian expression of mechano‐sensors and ARMM, and its disruption might be one of the causes of NOC …”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The Circadian expression of Piezo1, TRPV4, Connexin26, and VNUT, associated with the expression levels of the clock genes in mouse primary cultured urothelial cells

Ihara

Mitsui

Nakamura

et al. 2017

Neurourology and Urodynamics

Self Cite

View full text Add to dashboard Cite

show abstract

Recent advances in the pathophysiology of PIEZO1‐related hereditary xerocytosis

et al. 2021

View full text Add to dashboard Cite

Hereditary xerocytosis is a rare red blood cell disease related to gain-of-function mutations in the FAM38A gene, encoding PIEZO1, in 90% of cases; PIEZO1 is a broadly expressed mechano-transducer that plays a major role in many cell systems and tissues that respond to mechanical stress. In erythrocytes, PIEZO1 adapts the intracellular ionic content and cell hydration status to the mechanical constraints induced by the environment. Until recently, the pathophysiology of hereditary xerocytosis was mainly believed to be based on the "PIEZO1-Gardos channel axis" in erythrocytes, according to which PIEZO1-activating mutations induce a calcium influx that secondarily activates the Gardos channel, leading to potassium and water efflux and subsequently to red blood cell dehydration. However, recent studies have demonstrated additional roles for PIEZO1 during early erythropoiesis and reticulocyte maturation, as well as roles in other tissues and cells such as lymphatic vessels, hepatocytes, macrophages and platelets that may affect the pathophysiology of the disease. These findings, presented and discussed in this review, broaden our understanding of hereditary xerocytosis beyond that of primarily being a red blood cell disease and identify potential therapeutic targets. | INTRODUCTIONThe PIEZO proteins are a family of mechano-transducers first described in a neuron derived cell line in 2010. 1 The two members are PIEZO1, encoded by FAM38A on chromosome 16, and PIEZO2, encoded by FAM38B on chromosome 18. They are expressed in many tissues. 1,2 The structure of PIEZO1 has been recently elucidated. A first description of the murine protein revealed its three-dimensional structure, consisting of a three-bladed homotrimeric transmembrane helix completed by an extracellular cap. An intra-cytoplasmic domain, split into three parts, called "beams," extends from the transmembrane domain. The C-terminal end of each monomer has an extracellular domain (ECD), which forms the cap, and an intracellular domain (CTD), which appears to be connected to the paddles by the beams and closes the inner ion pore (Figure 1). The assembly provides a hydrophilic central transmembrane duct bordered by six helices that allows the passage of ions. Thus PIEZO1 constitutes a mechanosensitive ion channel due to the flexibility of the three blades. 1 Deformation of the plasma membrane subsequent to mechanical stimulation induces rotation of the PIEZO1 blades, transmitting such deformation to the ECD and CTD domains, allowing the ion channel to open using a lever-like mechanism. 2 When a compressive force is applied parallel to the axis of the ion channel, it induces lateral membrane tension, resulting in flattening and widening of PIEZO1, which causes the pore to open and allows the passage of ions. Such deformations are reversible, and PIEZO1 returns rapidly to its original conformation. [3][4][5] After opening, PIEZO1 acts as a passive channel for mono/divalent cations depending on their extracellular-intracellular Nicolas Jankovsky and Alexis Caulier...

show abstract

Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa

Cited by 36 publications

References 40 publications

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

The Circadian expression of Piezo1, TRPV4, Connexin26, and VNUT, associated with the expression levels of the clock genes in mouse primary cultured urothelial cells

Recent advances in the pathophysiology of PIEZO1‐related hereditary xerocytosis

Contact Info

Product

Resources

About