Predicted effect of circadian clock modulation of NHE3 of a proximal tubule cell on sodium transport

Wei, Ning; Gumz, Michelle L.

doi:10.1152/ajprenal.00008.2018

Cited by 30 publications

(24 citation statements)

References 49 publications

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“…Wrist skin temperature has been proposed as a new index for evaluating circadian system status [97]. Development of chronodisruption scores [98] and computational model of the renal circadian clock [99] would also facilitate clinical research. Longitudinal studies and ideally, interventional trials, would provide information on the causality and direction in the clinical association of disturbed sleep (a likely manifestation of chronodisruption) and CKD.…”

Section: The Way Forwardmentioning

confidence: 99%

Chronodisruption: A Poorly Recognized Feature of CKD

Carriazo

Ramos

Sanz

et al. 2020

Toxins

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Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

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Section: The Way Forwardmentioning

confidence: 99%

Chronodisruption: A Poorly Recognized Feature of CKD

Carriazo

Ramos

Sanz

et al. 2020

Toxins

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“…The present lung circadian clock model, inspired by Ref. [ 31 ], describes the time evolution of mRNA and corresponding protein concentrations of Per , Cry , Rev-Erb , Ror , and Bmal1 , and their modulation of proximal tubule epithelial transport [ 32 ]. Following the model assumptions in Ref.…”

Section: Methodsmentioning

confidence: 99%

“…Following the model assumptions in Ref. [ 31 ], we grouped the three Period homologs ( Per1-3 ) as a single Per gene and the two cryptochromes ( Cry1,2 ) as a single Cry gene. Similarly, the two isoforms Rev-Erbα and Rev-Erbβ and three isoforms Rora , Rorb and Rorc are represented by single variables Rev-Erb and Ror , respectively.…”

Section: Methodsmentioning

confidence: 99%

Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work

Abo

2021

PLoS Comput Biol

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The circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. Shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural light-dark cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model in the male and female rats. Shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at circadian time (CT) CT12 versus CT0 due to a dynamic change of Interleukin 10 (IL-10), an anti-inflammatory cytokine. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at CT0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.

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“…The present lung circadian clock model, inspired by Ref. [31], describes the time evolution of mRNA and corresponding protein concentrations of Per, Cry, Rev-Erb, Ror, and Bmal1. For simplicity, we grouped the three Period homologs (Per1-3 ) as a single Per gene and the two cryptochromes (Cry1,2 ) as a single Cry gene.…”

Section: Circadian Clock In the Lungmentioning

confidence: 99%

Modeling the circadian regulation of the immune system: sexually dimorphic effects of shift work

Abo

2020

Preprint

Self Cite

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The circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural sleep-wake cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model. shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at CT12 versus CT0 due to a change in the dynamics of IL-10. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at circadian time (CT) 0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.

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Predicted effect of circadian clock modulation of NHE3 of a proximal tubule cell on sodium transport

Cited by 30 publications

References 49 publications

Chronodisruption: A Poorly Recognized Feature of CKD

Chronodisruption: A Poorly Recognized Feature of CKD

Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work

Modeling the circadian regulation of the immune system: sexually dimorphic effects of shift work

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