دورية أكاديمية
Kidney-specific KO of the circadian clock protein PER1 alters renal Na + handling, aldosterone levels, and kidney/adrenal gene expression.
| العنوان: | Kidney-specific KO of the circadian clock protein PER1 alters renal Na + handling, aldosterone levels, and kidney/adrenal gene expression. |
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| المؤلفون: | Douma LG; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida., Costello HM; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Crislip GR; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Cheng KY; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Lynch IJ; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida.; North Florida/South Georgia Malcolm Randall Veterans Affairs Medical Center, Gainesville, Florida., Juffre A; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida., Barral D; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Masten S; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Roig E; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Beguiristain K; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Li W; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Bratanatawira P; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida., Wingo CS; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida.; North Florida/South Georgia Malcolm Randall Veterans Affairs Medical Center, Gainesville, Florida., Gumz ML; Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.; Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida.; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, Florida. |
| المصدر: | American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2022 Apr 01; Vol. 322 (4), pp. F449-F459. Date of Electronic Publication: 2022 Feb 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901990 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1466 (Electronic) Linking ISSN: 15221466 NLM ISO Abbreviation: Am J Physiol Renal Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, c1997- |
| مواضيع طبية MeSH: | Aldosterone*/blood , Circadian Clocks*/genetics , Hypertension* , Kidney*/metabolism , Period Circadian Proteins*/genetics , Period Circadian Proteins*/metabolism, Animals ; Cadherins/metabolism ; Gene Expression ; Male ; Mice ; Mice, Knockout ; Sodium/metabolism ; Sodium Chloride, Dietary/metabolism |
| مستخلص: | PERIOD 1 (PER1) is a circadian clock transcription factor that is regulated by aldosterone, a hormone that increases blood volume and Na + retention to increase blood pressure. Male global Per1 knockout (KO) mice develop reduced night/day differences in Na + excretion in response to a high-salt diet plus desoxycorticosterone pivalate treatment (HS + DOCP), a model of salt-sensitive hypertension. In addition, global Per1 KO mice exhibit higher aldosterone levels on a normal-salt diet. To determine the role of Per1 in the kidney, male kidney-specific Per1 KO (KS- Per1 KO) mice were generated using Ksp-cadherin Cre recombinase to remove exons 2-8 of Per1 in the distal nephron and collecting duct. Male KS- Per1 KO mice have increased Na + retention but have normal diurnal differences in Na + excretion in response to HS + DOCP. The increased Na + retention is associated with altered expression of glucocorticoid and mineralocorticoid receptors, increased serum aldosterone, and increased medullary endothelin-1 compared with control mice. Adrenal gland gene expression analysis revealed that circadian clock and aldosterone synthesis genes have altered expression in KS- Per1 KO mice compared with control mice. These results emphasize the importance of the circadian clock not only in maintaining rhythms of physiological functions but also for adaptability in response to environmental cues, such as HS + DOCP, to maintain overall homeostasis. Given the prevalence of salt-sensitive hypertension in the general population, these findings have important implications for our understanding of how circadian clock proteins regulate homeostasis. NEW & NOTEWORTHY For the first time, we show that knockout of the circadian clock transcription factor PERIOD 1 using kidney-specific cadherin Cre results in increased renal Na + reabsorption, increased aldosterone levels, and changes in gene expression in both the kidney and adrenal gland. Diurnal changes in renal Na + excretion were not observed, demonstrating that the clock protein PER1 in the kidney is important for maintaining homeostasis and that this effect may be independent of time of day. |
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| معلومات مُعتمدة: | R01 DK109570 United States DK NIDDK NIH HHS; F32 DK121424 United States DK NIDDK NIH HHS; T32 DK104721 United States DK NIDDK NIH HHS; R03 DK098460 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: circadian rhythm; homeostasis; salt; sodium |
| سلسلة جزيئية: | figshare 10.6084/m9.figshare.18416846.v1 |
| المشرفين على المادة: | 0 (Cadherins) 0 (Per1 protein, mouse) 0 (Period Circadian Proteins) 0 (Sodium Chloride, Dietary) 4964P6T9RB (Aldosterone) 9NEZ333N27 (Sodium) |
| تواريخ الأحداث: | Date Created: 20220207 Date Completed: 20220504 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC9169971 |
| DOI: | 10.1152/ajprenal.00385.2021 |
| PMID: | 35129370 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1466 |
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| DOI: | 10.1152/ajprenal.00385.2021 |