Local receptors as novel regulators for peripheral clock expression

Abstract

Mammalian circadian control is determined by a central clock in the brain suprachiasmatic nucleus (SCN) and synchronized peripheral clocks in other tissues. Increasing evidence suggests that SCN-independent regulation of peripheral clocks also occurs. We examined how activation of excitatory receptors influences the clock protein PERIOD 2 (PER2) in a contractile organ, the urinary bladder. PERIOD2::LUCIFERASE-knock-in mice were used to report real-time PER2 circadian dynamics in the bladder tissue. Rhythmic PER2 activities occurred in the bladder wall with a cycle of ∼24 h and peak at ∼12 h. Activation of the muscarinic and purinergic receptors by agonists shifted the peak to an earlier time (7.2±2.0 and 7.2±0.9 h, respectively). PER2 expression was also sensitive to mechanical stimulation. Aging significantly dampened PER2 expression and its response to the agonists. Finally, muscarinic agonist-induced smooth muscle contraction also exhibited circadian rhythm. These data identified novel regulators, endogenous receptors, in determining local clock activity, in addition to mediating the central control. Furthermore, the local clock appears to reciprocally align receptor activity to circadian rhythm for muscle contraction. The interaction between receptors and peripheral clock represents an important mechanism for maintaining physiological functions and its dysregulation may contribute to age-related organ disorders.—Wu, C., Sui, G., Archer, S. N., Sassone-Corsi, P., Aitken, K., Bagli, D., Chen, Y. Local receptors as novel regulators for peripheral clock expression.

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

“…We suggest that crosstalk between epithelial cell layer to submucosal and smooth muscle layer may have important role to create a typical circadian clock. In addition to the reciprocal interaction between the master clock in SCN and peripheral tissues, the local receptors expressed in bladder tissue were reported to mediate the entrainment of peripheral circadian clock . However, the previous study used ex vivo bladder mucosa, which included different cell types from the epithelial cell layer to the submucosal layer.…”

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

“…Our findings are also corroborated by data in human studies. The expression of key clock genes and their proteins found in rodent bladders is also shown in human bladder tissues . Furthermore, circadian dysregulation may also cause bladder pathologies in humans including bladder cancer, prostate cancer, LUTS, nocturia, and overactive bladder .…”

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

“…The timing of protein expression after the transcription of mechanosensor, Cx26 and VNUT mRNAs also seemed to be simultaneous in the bladder mucosa. In addition, receptors in the bladder, the functions of which change with circadian rhythms, were previously reported to act as regulators of circadian rhythms in the local area [38]. Possibly, circadian gene expression processes of mechanosensor, Cx26 and VNUT under the regulation of clock genes may dominate substantial role to create circadian function of bladder, although another factors that contribute to maintain circadian rhythm could exists in the bladder.…”