Plasma corticosterone rhythmicity loss dysregulates the renal artery circadian transcriptome and abolishes daily vasodilation variation

Autor: Georgios Krilis, Frances Turner, Hannah Costello, Matthew Bailey, Jessica Ivy
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5784734
Popis: Molecular clocks control a daily transcriptional schedule that maintains tissue homeostasis. Glucocorticoids synchronize peripheral clocks with the master clock in the suprachiasmatic nucleus in response to ambient light. In humans and mice, arrhythmic glucocorticoids induce non-dipping blood pressure and vascular dysfunction. The mechanisms of this are poorly understood. We hypothesize that arrhythmic activation of the glucocorticoid receptor desynchronizes the molecular clock mechanism in the renal artery, a major component of blood pressure control, dysregulating normal function. Our aim was to dissect renal artery circadian physiology transcriptionally and functionally and interrogate the effect of arrhythmic glucocorticoids. Male mice, kept on a 12:12 light:dark cycle, were anesthetised with 4% isolflurane and implanted with a hypodermal pellet containing either vehicle or corticosterone (≈3.7 mg/kg per day), to flatten the endogenous glucocorticoid rhythm. After 7 days, mice were culled by cervical dislocation at 2hr intervals for 48 hours and the renal arteries taken. The renal artery circadian transcriptome was profiled using Illumina Truseq Stranded RNA-sequencing. Cosinor regression (Limorhyde) was applied to the control group and identified 465 of 14425 (~3%) protein coding transcripts with rhythmic expression (p This study was funded by the British Heart Foundation (PhD studentship code: FS/18/57/34178) and the Kidney Research UK (Intermediate Grant Code: INT_001_20181115 and IN_002_2021 0729). Analyses were carried out by Edinburgh Genomics at the University of Edinburgh. Edinburgh Genomics is partly supported through core grants from NERC (R8/H10/56), MRC (MR/K001744/1) and BBSRC (BB/J004243/1). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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