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Article ; Online: Circadian regulation of renal function.

Johnston, Jermaine G / Pollock, David M

2018 Volume 119, Page(s) 93–107

Abstract: ... genes on renal function, at the molecular and physiological level, independent of other external factors ... regulation in the kidney from basic and clinical research in order to provide a foundation on which a great ... in recent years has unveiled previously underappreciated depth of influence by circadian rhythms and clock ...

Abstract	The kidneys regulate many vital functions that require precise control throughout the day. These functions, such as maintaining sodium balance or regulating arterial pressure, rely on an intrinsic clock mechanism that was commonly believed to be controlled by the central nervous system. Mounting evidence in recent years has unveiled previously underappreciated depth of influence by circadian rhythms and clock genes on renal function, at the molecular and physiological level, independent of other external factors. The impact of circadian rhythms in the kidney also affects individuals from a clinical standpoint, as the loss of rhythmic activity or clock gene expression have been documented in various cardiovascular diseases. Fortunately, the prognostic value of examining circadian rhythms may prove useful in determining the progression of a kidney-related disease, and chronotherapy is a clinical intervention that requires consideration of circadian and diurnal rhythms in the kidney. In this review, we discuss evidence of circadian regulation in the kidney from basic and clinical research in order to provide a foundation on which a great deal of future research is needed to expand our understanding of circadian relevant biology.
MeSH term(s)	Animals ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Humans ; Kidney/physiology ; Renal Insufficiency, Chronic/physiopathology
Language	English
Publishing date	2018-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2018.01.018
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Article ; Online: Circadian regulation of renal function.

Firsov, Dmitri / Bonny, Olivier

Kidney international

2010 Volume 78, Issue 7, Page(s) 640–645

Abstract: ... of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and ... including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance ... other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed ...

Abstract	Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms.
MeSH term(s)	Animals ; Circadian Clocks ; Circadian Rhythm/physiology ; Erythropoietin/physiology ; Homeostasis ; Humans ; Kidney/physiology ; Water-Electrolyte Balance
Chemical Substances	Erythropoietin (11096-26-7)
Language	English
Publishing date	2010-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1038/ki.2010.227
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Article ; Online: Circadian regulation of renal function and potential role in hypertension.

Bonny, Olivier / Firsov, Dmitri

Current opinion in nephrology and hypertension

2013 Volume 22, Issue 4, Page(s) 439–444

Abstract: ... research points to the major role of circadian rhythms in renal function and in control of blood pressure. ... involved in renal homeostatic functions have been shown to exhibit significant circadian oscillation ... Purpose of review: Previous studies have shown that a variety of specific renal functions exhibit ...

Abstract	Purpose of review: Previous studies have shown that a variety of specific renal functions exhibit circadian oscillations. This review aims to provide an update on the molecular mechanisms underlying circadian rhythms in the kidney, and to discuss how dysregulation of circadian rhythms can interfere with kidney function. Recent findings: The molecular mechanism responsible for generating and maintaining circadian rhythms has been unraveled in great detail. This mechanism, known as the circadian clock, drives circadian oscillation in expression levels of a large number of renal mRNA transcripts. Several proteins critically involved in renal homeostatic functions have been shown to exhibit significant circadian oscillation in their expression levels or in their posttranslational modifications. In transgenic mouse models, disruption of circadian clock activity results in dramatic changes in the circadian pattern of urinary sodium and potassium excretion and causes significant changes in arterial blood pressure. A growing amount of evidence suggests that dysregulation of circadian rhythms is associated with the development of hypertension and accelerated progression of chronic kidney disease and cardiovascular disease in humans. Chronotherapy studies have shown that the efficacy of antihypertensive medication is greatly dependent on the circadian time of drug administration. Summary: Recent research points to the major role of circadian rhythms in renal function and in control of blood pressure.
MeSH term(s)	Animals ; Antihypertensive Agents/administration & dosage ; Blood Pressure/drug effects ; Circadian Rhythm ; Circadian Rhythm Signaling Peptides and Proteins/genetics ; Circadian Rhythm Signaling Peptides and Proteins/metabolism ; Drug Chronotherapy ; Gene Expression Regulation ; Humans ; Hypertension/drug therapy ; Hypertension/genetics ; Hypertension/metabolism ; Hypertension/physiopathology ; Kidney/drug effects ; Kidney/metabolism ; Kidney/physiopathology ; Signal Transduction
Chemical Substances	Antihypertensive Agents ; Circadian Rhythm Signaling Peptides and Proteins
Language	English
Publishing date	2013-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0b013e32836213b8
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Zs.A 3686: Show issues

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Article ; Online: The circadian rhythm key gene

Wu, Gujie / Ren, Hefei / Hu, Qin / Ma, Huiyun / Chen, Hongyu / Zhou, Lin / Xu, Kun / Ding, Liang

Frontiers in immunology

2023 Volume 14, Page(s) 1115809

Abstract: ... the circadian rhythm. ARNTL2 plays an important role in human biological functions. However, its role in various tumors ... we found that ARNTL2 not only regulates cell cycle-related functions to promote cell proliferation but also ... regulates autoimmunity-related functions of the innate and adaptive immune systems, and other immune-related ...

Abstract	Background: Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) belongs to the b HLH- PAS domain transcription factor family and is one of the key clock genes that control the circadian rhythm. ARNTL2 plays an important role in human biological functions. However, its role in various tumors, especially in the tumor immune microenvironment (TIME) and immunotherapy, remains unclear. Methods: We integrated data from cancer patients from multiple databases, including the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI, with data from a large clinical study, three immunotherapy cohorts, and Results: ARNTL2 displayed abnormal expression within most malignant tumors, and is significantly associated with poorer survival and pathologic staging. Through gene-set enrichment analysis (GSEA) and gene-set variation analysis (GSVA), we found that ARNTL2 not only regulates cell cycle-related functions to promote cell proliferation but also regulates autoimmunity-related functions of the innate and adaptive immune systems, and other immune-related signaling pathways. In addition, ARNTL2 overexpression contributes to an immunosuppressive tumor microenvironment that plays a key role in immunosuppression-related features, such as the expression of immunosuppression-related genes and pathways and the number of immunosuppressive-infiltrating cells, including regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). The group of patients with low ARNTL2 expression who received immune checkpoint inhibitors (ICI) therapy had better response rates and longer survival when compared to those with high ARNTL2 expression. Conclusion: The findings of this study suggest that ARNTL2 is a potential human oncogene that plays an important role in tumorigenesis and cancer immunity. Elevated ARNTL2 expression indicates an immunosuppressive tumor microenvironment. Targeting ARNTL2 in combination with ICI therapy could bring more significant therapeutic benefits to patients with cancer. Our study sheds light on the remarkable potential of ARNTL2 in tumor immunity and provides a novel perspective for anti-tumor strategies.
MeSH term(s)	Humans ; Cell Line, Tumor ; ARNTL Transcription Factors/genetics ; Prognosis ; Protein Interaction Maps ; Signal Transduction ; Tumor Microenvironment ; Immunotherapy ; Treatment Outcome ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Up-Regulation ; Biomarkers ; Biomarkers, Tumor/genetics
Chemical Substances	BMAL2 protein, human ; ARNTL Transcription Factors ; Biomarkers ; Biomarkers, Tumor
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1115809
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Article ; Online: Recent advances in understanding the kidney circadian clock mechanism.

Juffre, Alexandria / Gumz, Michelle L

American journal of physiology. Renal physiology

2024 Volume 326, Issue 3, Page(s) F382–F393

Abstract: ... all of which display circadian rhythmicity. For this reason, studying the circadian regulation of the kidney is ... circadian regulation within the kidney. In this review, the current knowledge regarding circadian ... rhythms in the kidney is explored, focusing on the molecular clock machinery, circadian control of renal functions, and ...

Abstract	Circadian rhythms are endogenous biological oscillations that regulate various physiological processes in organisms, including kidney function. The kidney plays a vital role in maintaining homeostasis by regulating water and electrolyte balance, blood pressure, and excretion of metabolic waste products, all of which display circadian rhythmicity. For this reason, studying the circadian regulation of the kidney is important, and the time of day is a biological and experimental variable that must be considered. Over the past decade, considerable progress has been made in understanding the molecular mechanisms underlying circadian regulation within the kidney. In this review, the current knowledge regarding circadian rhythms in the kidney is explored, focusing on the molecular clock machinery, circadian control of renal functions, and the impact of disrupted circadian rhythms on kidney health. In addition, parameters that should be considered and future directions are outlined in this review.
MeSH term(s)	Circadian Clocks ; Kidney/metabolism ; Circadian Rhythm/physiology ; Water-Electrolyte Balance ; Homeostasis
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00214.2023
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Article ; Online: The role of renal circadian biorhythms in lifelong LUTS.

Hervé, François / Vande Walle, Johan / Raes, Ann / Haddad, Rebecca / Monaghan, Thomas / Drake, Marcus J / Kamperis, Konstantinos / Dossche, Lien / Zipkin, Jacob / Weiss, Jeffrey / Verbakel, Irina / Bou Kheir, George / Everaert, Karel

Neurourology and urodynamics

2023 Volume 43, Issue 5, Page(s) 1109–1117

Abstract: ... It explores circadian regulation of urine production, maturation of renal function from birth to adulthood ... presented during a webinar and subsequent discussions.: Results: Renal function undergoes significant ... For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing ...

Abstract	Introduction: This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. Methods: An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. Results: Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. Conclusion: The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.
MeSH term(s)	Humans ; Circadian Rhythm/physiology ; Lower Urinary Tract Symptoms/physiopathology ; Lower Urinary Tract Symptoms/etiology ; Kidney/physiopathology ; Aging/physiology ; Diuresis ; Adult ; Adolescent
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.25308
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Article ; Online: Loss of circadian gene

Zhang, Dingguo / Jin, Chunhua / Obi, Ijeoma E / Rhoads, Megan K / Soliman, Reham H / Sedaka, Randee S / Allan, J Miller / Tao, Binli / Speed, Joshua S / Pollock, Jennifer S / Pollock, David M

American journal of physiology. Renal physiology

2020 Volume 318, Issue 3, Page(s) F710–F719

Abstract: Kidney function follows a 24-h rhythm subject to regulation by circadian genes including ...

Abstract	Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor
MeSH term(s)	ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; Aldosterone/metabolism ; Aldosterone/urine ; Animals ; Blood Pressure/physiology ; Female ; Gene Expression Regulation/physiology ; Kidney Tubules, Collecting/metabolism ; Male ; Mice ; Mice, Knockout ; Potassium/urine ; Receptor, Endothelin B/genetics ; Receptor, Endothelin B/metabolism ; Sex Factors ; Sodium/metabolism ; Sodium/urine ; Sodium Chloride, Dietary/administration & dosage
Chemical Substances	ARNTL Transcription Factors ; Bmal1 protein, mouse ; Receptor, Endothelin B ; Sodium Chloride, Dietary ; Aldosterone (4964P6T9RB) ; Sodium (9NEZ333N27) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2020-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00364.2019
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Article ; Online: Circadian clocks of the kidney: function, mechanism, and regulation.

Costello, Hannah M / Johnston, Jermaine G / Juffre, Alexandria / Crislip, G Ryan / Gumz, Michelle L

Physiological reviews

2022 Volume 102, Issue 4, Page(s) 1669–1701

Abstract: ... circadian clocks within the cells of the kidney contribute to the regulation of a variety of renal processes ... signals, on kidney function is also reviewed. Circadian rhythms in renal function are an integral part ... In this review, we summarize what is currently known regarding the function, mechanism, and regulation of kidney ...

Abstract	An intrinsic cellular circadian clock is located in nearly every cell of the body. The peripheral circadian clocks within the cells of the kidney contribute to the regulation of a variety of renal processes. In this review, we summarize what is currently known regarding the function, mechanism, and regulation of kidney clocks. Additionally, the effect of extrarenal physiological processes, such as endocrine and neuronal signals, on kidney function is also reviewed. Circadian rhythms in renal function are an integral part of kidney physiology, underscoring the importance of considering time of day as a key biological variable. The field of circadian renal physiology is of tremendous relevance, but with limited physiological and mechanistic information on the kidney clocks this is an area in need of extensive investigation.
MeSH term(s)	Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Endocrine System ; Humans ; Kidney/physiology
Language	English
Publishing date	2022-05-16
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00045.2021
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Article ; Online: Sex differences in circadian regulation of kidney function of the mouse.

Layton, Anita T / Gumz, Michelle L

American journal of physiology. Renal physiology

2022 Volume 323, Issue 6, Page(s) F675–F685

Abstract: ... exhibit circadian rhythms. Interestingly, the circadian regulation of these transporters appears to be ... Kidney function is regulated by the circadian clock. Not only do glomerular filtration rate and ... that represent the effects of sex and the circadian clock on renal hemodynamics and transporter activity ...

Abstract	Kidney function is regulated by the circadian clock. Not only do glomerular filtration rate and urinary excretion oscillate during the day, but the expressions of several renal transporter proteins also exhibit circadian rhythms. Interestingly, the circadian regulation of these transporters appears to be sexually dimorphic. Thus, the goal of the present study was to investigate the mechanisms by which the kidney function of the mouse is modulated by sex and time of day. To accomplish this, we developed the first computational models of epithelial water and solute transport along the mouse nephrons that represent the effects of sex and the circadian clock on renal hemodynamics and transporter activity. We conducted simulations to study how the circadian control of renal transport genes affects overall kidney function and how that process differs between male and female mice. Simulation results predicted that tubular transport differs substantially among segments, with relative variations in water and Na
MeSH term(s)	Mice ; Female ; Male ; Animals ; Sex Characteristics ; ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; Nephrons/metabolism ; Sodium/metabolism ; Circadian Rhythm/genetics ; Kidney/metabolism ; Membrane Transport Proteins/metabolism ; Water/metabolism
Chemical Substances	ARNTL Transcription Factors ; Sodium (9NEZ333N27) ; Membrane Transport Proteins ; Water (059QF0KO0R)
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00227.2022
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Article ; Online: Intrauterine and early-life malnutrition in rats disrupts the circadian rhythm programming of energy metabolites through adulthood.

Bustamante-Valdez, Dulce Jocelyn / Fuentes-Cano, Martin Alejandro / Gonzalez-Ruano, Jesus Salvador / Martinez-Canabal, Alonso / Cardenas-Vazquez, Rene / Duran, Pilar

PloS one

2024 Volume 19, Issue 3, Page(s) e0299554

Abstract: ... for correct interaction with the environment and physiological regulation. Exposure to malnutrition during ... on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental ... malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators ...

Abstract	Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. "Cafeteria diet" has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan.
MeSH term(s)	Pregnancy ; Female ; Rats ; Animals ; Humans ; Circadian Rhythm/physiology ; Insulin ; Malnutrition ; Triglycerides ; Diet, High-Fat/adverse effects ; Glucose ; Prenatal Exposure Delayed Effects ; Mammals
Chemical Substances	Insulin ; Triglycerides ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0299554
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