Recent advances in understanding the circadian clock in renal physiology

Crislip, G. Ryan; Masten, Sarah; Gumz, Michelle L.

doi:10.1016/j.cophys.2018.06.002

Cited by 11 publications

(9 citation statements)

References 63 publications

(84 reference statements)

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“…It has also been demonstrated that the pineal gland of rats controls the ion-excretory function of the kidneys and the circadian rhythm of diuresis. Additionally, exogenous light stimuli, forming the daily rhythm of the kidneys, are mediated through the pineal gland [ 34 ]. The light–dark cycle is the main synchronizer of circadian rhythms in the excretion of water and electrolytes.…”

Section: Discussionmentioning

confidence: 99%

Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

et al. 2022

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Artificial light is characterized by certain features of its impact on the body in terms of its spectral distribution of power, duration of exposure and intensity. Short waves, perceived as blue light, are the strongest synchronizing agent for the circadian system. In the present work, we investigated the features of the circadian rhythms of blood pressure (BP), heart rate (HR), the excretion of electrolytes and the secretion of melatonin in normotensive (Wistar–Kyoto) and hypertensive (SHR) rats under the action of monochromatic blue light in the daytime period. It was found that the exposure of Wistar–Kyoto rats to monochromatic blue light was accompanied by a significant decrease in nighttime and 24h systolic BP. The most remarkable changes are characteristic of the HR in SHR rats under monochromatic light. A significant decrease in HR in each time period was found, but the predominance of nighttime over daytime values remained in SHR animals. There was also a significant increase in the mesor of the HR in SHR rats. Additionally, the amplitude of diastolic BP and HR, as well as the range of oscillations in HR, were significantly increased compared with the standard light pattern. In contrast to SHR rats, the regulation of the circadian rhythms in Wistar–Kyoto rats was more flexible and presented more changes, which may be aimed at the adaptation of the body to environmental conditions. For Wistar–Kyoto rats, an increase in the level of excreted electrolytes was observed under the action of monochromatic light, but no similar changes were found in SHR rats. For Wistar–Kyoto rats, a significant decrease in the urine concentration of aMT6s in the daytime and nighttime periods is characteristic, which results in the loss of the circadian rhythm. In SHR rats, there was a significant decrease in the nighttime content of aMT6s in the urine, while the daytime concentration, on the contrary, increased. The obtained data demonstrate that prolonged exposure to monochromatic blue light in the daytime period affects the circadian structure of the rhythms of the cardiovascular system, the rhythm of electrolyte excretion and the production of epiphyseal melatonin in wild-type and hypertensive animals. In SHR rats, the rhythms of BP and HR exhibit a more rigid pattern.

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Section: Discussionmentioning

confidence: 99%

Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

et al. 2022

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“…Accumulating studies have examined the role of circadian clock in renal function. 28,29 Among the canonical clock genes, Bmal1 is the only one whose sole deletion results in complete loss of circadian rhythms. 30 Most recent research has addressed that Bmal1 plays pivotal roles in renal physiological functions.…”

Section: Discussionmentioning

confidence: 99%

Postnatal deletion of Bmal1 in mice protects against obstructive renal fibrosis via suppressing Gli2 transcription

et al. 2021

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Circadian clock is involved in regulating most renal physiological functions, including water and electrolyte balance and blood pressure homeostasis, however, the role of circadian clock in renal pathophysiology remains largely unknown. Here we aimed to investigate the role of Bmal1, a core clock component, in the development of renal fibrosis, the hallmark of pathological features in many renal diseases. The inducible Bmal1 knockout mice (iKO) whose gene deletion occurred in adulthood were used in the study. Analysis of the urinary water, sodium and potassium excretion showed that the iKO mice exhibit abolished diurnal variations. In the model of renal fibrosis induced by unilateral ureteral obstruction, the iKO mice displayed significantly decreased tubulointerstitial fibrosis reflected by attenuated collagen deposition and mitigated expression of fibrotic markers α-SMA and fibronectin. The hedgehog pathway transcriptional effectors Gli1 and Gli2, which have been reported to be involved in the pathogenesis of renal fibrosis, were significantly decreased in the iKO mice. Mechanistically, ChIP assay and luciferase reporter assay revealed that BMAL1 bound to the promoter of and activate the transcription of Gli2, but not Gli1, suggesting that the involvement of Bmal1 in renal fibrosis was possibly mediated via Gli2-dependent mechanisms. Furthermore, treatment with TGF-β increased Bmal1 in cultured murine proximal tubular cells. Knockdown of Bmal1 abolished, while overexpression of Bmal1 increased, Gli2 and the expression of fibrosis-related genes. Collectively, these results revealed a prominent role of the core clock gene Bmal1 in tubulointerstitial fibrosis. Moreover, we identified Gli2 as a novel target of Bmal1, which may mediate the adverse effect of Bmal1 in obstructive nephropathy.

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“…Circadian transcription factors influence renal function (11) and BP (12). The DCT expresses the canonical circadian transcription factors period circadian protein homolog 1 (Per1), Per2, aryl hydrocarbon receptor nuclear translocatorlike protein (Arntl or Bmal1), Clock, and cryptochrome 1/2 (Cry1 and Cry2) (54).…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid receptor activation stimulates the sodium-chloride cotransporter and influences the diurnal rhythm of its phosphorylation

Ivy

Jones

Costello

et al. 2019

American Journal of Physiology-Renal Physiology

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The sodium-chloride cotransporter (NCC) in the distal convoluted tubule contributes importantly to sodium balance and blood pressure (BP) regulation. NCC phosphorylation determines transport activity and has a diurnal rhythm influenced by glucocorticoids. Disturbing this rhythm induces “nondipping” BP, an abnormality that increases cardiovascular risk. The receptor through which glucocorticoids regulate NCC is not known. In this study, we found that acute administration of corticosterone to male C57BL6 mice doubled NCC phosphorylation without affecting total NCC abundance in both adrenalectomized and adrenal-intact mice. Corticosterone also increased the whole kidney expression of canonical clock genes: period circadian protein homolog 1 ( Per1), Per2, cryptochrome 1, and aryl hydrocarbon receptor nuclear translocator-like protein 1. In adrenal-intact mice, chronic blockade of glucocorticoid receptor (GR) with RU486 did not change total NCC but prevented corticosterone-induced NCC phosphorylation and activation of clock genes. Blockade of mineralocorticoid receptor (MR) with spironolactone reduced the total pool of NCC but did not affect stimulation by corticosterone. The diurnal rhythm of NCC phosphorylation, measured at 6-h intervals, was blunted by chronic GR blockade, and a similar dampening of diurnal variation was seen in GR heterozygous null mice. These effects on NCC phosphorylation did not reflect altered rhythmicity of plasma corticosterone or serum and glucocorticoid-induced kinase 1 activity. Both mineralocorticoids and glucocorticoids emerge as regulators of NCC, acting via distinct receptor pathways. MR activation provides maintenance of the NCC protein pool; GR activation dynamically regulates NCC phosphorylation and establishes the diurnal rhythm of NCC activity. This study has implications for circadian BP homeostasis, particularly in individuals with abnormal glucocorticoid signaling as is found in chronic stress and corticosteroid therapy.

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Recent advances in understanding the circadian clock in renal physiology

Abstract: Accumulating evidence suggests a critical role for the molecular circadian clock in the regulation of renal function. Here, we consider the most recent advances in our understanding of the relationship between the circadian clock and renal physiology.

Cited by 11 publications

References 63 publications

Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

Postnatal deletion of Bmal1 in mice protects against obstructive renal fibrosis via suppressing Gli2 transcription

Glucocorticoid receptor activation stimulates the sodium-chloride cotransporter and influences the diurnal rhythm of its phosphorylation

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