Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice

Ihara, Takeshi; Mitsui, Takahiko; Shimura, Hiroshi; Tsuchiya, Satoshi; Kanda, Mie; Kira, Satoru; Nakagomi, Hiroshi; Sawada, Norifumi; Kamiyama, Manabu; Shigetomi, Eiji; Shinozaki, Yukiko; Koizumi, Schuichi; Takeda, Masayuki

doi:10.1016/j.lfs.2021.119555

Cited by 12 publications

(9 citation statements)

References 41 publications

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“…GsMTx4 has been used to study the functional role of cationic mechanosensitive channels, especially in muscle tissue. The sensitivity of the Piezo channel to double-layer stress and its mechanical sensitivity in heterologous systems are key aspects ( Li et al, 2019 ; Ihara et al, 2021 ) to determining the mechanism of GsMTx4 action. Through a literature review, we found that GxMTx4 has a better inhibitory effect, so we chose to inject GxMTx4 to achieve the experimental goals.…”

Section: Discussionmentioning

confidence: 99%

Piezo1 Affects Temporomandibular Joint Osteoarthritis by Influencing pSmad3

Ma²,

Ma³

et al. 2022

Front. Physiol.

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Objective: The aim of this research was to study the expression of Piezo1 in a rat temporomandibular joint osteoarthritis animal model and to explore its mechanism for inducing inflammatory changes.Methods: A total of 24male SD rats aged approximately 8 weeks were randomly divided into three groups: the blank control group, complete Freund’s adjuvant group (CFA), and CFA + inhibitor (GsMTx4) group. After 3 weeks, the condylar heads of the rats were evaluated by micro-CT, HE, immunohistochemistry, safranin O staining, and other experimental techniques. Protein was extracted from the subchondral bone, and the changes in Piezo1, Smad3, and pSmad3 levels in each group were detected by Western blotting. p < 0.05 was considered to indicate statistical significance.Results: The degree of damage to the cartilage and subchondral bone in the Piezo1 inhibitor group was smaller than that in the CFA group. The expression level of Piezo1 in the CFA group was higher than that in the other groups, and the difference was statistically significant. The expression of pSmad3 in the CFA group was also higher than that in the other groups (p < 0.05).Conclusion: Piezo1 is expressed in the condylar cartilage and subchondral bone of rats, and the degree of condylar destruction can be improved by influencing the pSmad3 expression.

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Section: Discussionmentioning

confidence: 99%

Piezo1 Affects Temporomandibular Joint Osteoarthritis by Influencing pSmad3

Ma²,

Ma³

et al. 2022

Front. Physiol.

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“…Nocturia (waking up at night more than once to void 55 ), is a chronic condition affecting up to 75–90% of the elderly population 56 . The circadian rhythms disturbances including impaired circadian peripheral clock in the bladder, melatonin production, and sleep disturbance are suggested as main causes of the disease 4 , 6 , 20 , 51 . Endogenous melatonin levels decrease with age 57 .…”

Section: Discussionmentioning

confidence: 99%

“…Circadian rhythms are orchestrated by a transcriptional-translational feedback loop for a set of oscillating circadian ‘clock’ genes within the “master clock” located in a region of the anterior hypothalamus, the suprachiasmatic nucleus (SCN) 2 , 3 . The central master clock can influence the circadian systems found in most peripheral tissues and organs (termed “peripheral clocks”) such as gut, liver, adipose tissue, immune cells, bladder, and others 1 , 2 , 4 – 7 . The hormone melatonin ( N -acetyl-5-methoxytryptamine) is produced and released primarily during darkness by pinealocytes of the pineal gland and is involved in the synchronisation of the peripheral clocks by the central clock and serves as feedback mechanisms for SCN neurons 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Ramsay

Zagorodnyuk

2022

Sci Rep

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Melatonin is a circadian rhythm regulator capable of controlling a variety of physiological processes in the body. It predominantly acts via the melatonin 1 (MT1) and MT2 receptors expressed in the CNS neurons and peripheral organs and tissues. Melatonin can modulate urinary bladder function, however, to date it is not known if melatonin can regulate activity of sensory neurons innervating the bladder. Bladder afferents play an important role in urine storage and voiding. Therefore, this study aims to determine if melatonin can regulate mechanosensitivity of 2 major classes of sensory neurons in the guinea pig bladder: stretch-insensitive mucosal and low threshold stretch-sensitive muscular-mucosal afferents. The effects of melatonin on the mechanosensitivity of mucosal and muscular-mucosal afferents were measured ex vivo using single unit extracellular recording. Melatonin did not affect the responses of mucosal afferents to stroking of their receptive fields but did concentration-dependently, significantly inhibit 69% of muscular-mucosal afferents responses to stroking and bladder stretch. This inhibitory effect was not affected by the MT1 receptor antagonist, S26131 but was blocked by the selective MT2 receptor antagonists, K-185 and 4-P-PDOT. Forskolin significantly potentiated the responses of muscular-mucosal afferents to stroking and stretch, which were prevented by melatonin. These findings demonstrate a direct inhibitory effect of melatonin on the mechanosensitivity of low threshold stretch-sensitive muscular-mucosal bladder afferents acting via MT2 receptors, which is independent from its action on detrusor muscle. This may have important clinical implications for the treatment of many common bladder disorders including nocturia.

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“…Experimental evidence by chromatin immunoprecipitation suggested that the clock protein binds to the promoters of Piezo1 and TRPV4 to regulate transcription 87 . More critically, the role of GsMTx4 in lowering urine sensation in wild-type mice is related to the expression levels of the circadian clock and Piezo1 90 . The maximum effect is exerted during the sleep phase 90 .…”

Section: Roles Of Piezo Channels In the Urinary Systemmentioning

confidence: 99%

“…More critically, the role of GsMTx4 in lowering urine sensation in wild-type mice is related to the expression levels of the circadian clock and Piezo1 90 . The maximum effect is exerted during the sleep phase 90 . In this sense, reshaping the circadian rhythm of urinary function by inhibiting the Piezo1 channel might become a new treatment strategy for nocturia.…”

Section: Roles Of Piezo Channels In the Urinary Systemmentioning

confidence: 99%

Piezo channels in the urinary system

Zhao

et al. 2022

Exp Mol Med

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The Piezo channel family, including Piezo1 and Piezo2, includes essential mechanosensitive transduction molecules in mammals. Functioning in the conversion of mechanical signals to biological signals to regulate a plethora of physiological processes, Piezo channels, which have a unique homotrimeric three-blade propeller-shaped structure, utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways. Piezo channels have a wide range of biological roles in various human systems, both in vitro and in vivo. Currently, there is a lack of comprehensive understanding of their antagonists and agonists, and therefore further investigation is needed. Remarkably, increasingly compelling evidence demonstrates that Piezo channel function in the urinary system is important. This review article systematically summarizes the existing evidence of the importance of Piezo channels, including protein structure, mechanogating mechanisms, and pharmacological characteristics, with a particular focus on their physiological and pathophysiological roles in the urinary system. Collectively, this review aims to provide a direction for future clinical applications in urinary system diseases.

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Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice

Cited by 12 publications

References 41 publications

Piezo1 Affects Temporomandibular Joint Osteoarthritis by Influencing pSmad3

Piezo1 Affects Temporomandibular Joint Osteoarthritis by Influencing pSmad3

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Piezo channels in the urinary system

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