The glomerular circadian clock temporally regulates basement membrane dynamics and the podocyte glucocorticoid response.

Autor:	Preston R; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Chrisp R; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Dudek M; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Morais MRPT; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Tian P; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Williams E; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Naylor RW; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Davenport B; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Pathiranage DRJ; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Benson E; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Spiller DG; Bioimaging Core Facility, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK., Bagnall J; Bioimaging Core Facility, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK., Zeef L; Bioinformatics Core Facility, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK., Lawless C; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Baker SM; Bioinformatics Core Facility, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK., Meng QJ; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: Qing-Jun.Meng@manchester.ac.uk., Lennon R; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Department of Pediatric Nephrology, Royal Manchester Children's Hospital, Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: Rachel.lennon@manchester.ac.uk.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2024 Nov 06. Date of Electronic Publication: 2024 Nov 06.
DOI:	10.1016/j.kint.2024.10.016
Abstrakt:	Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation. With clock gene reporter mice, cell-autonomous glomerular clocks which likely govern rhythmic fluctuations in glomerular physiology were identified. Using circadian time-series transcriptomic profiling, the first circadian glomerular transcriptome with 375 rhythmic transcripts, enriched for extracellular matrix and glucocorticoid receptor signaling ontologies, were identified. Subsets of rhythmic matrix-related genes required for basement membrane assembly and turnover, and circadian variation in matrix ultrastructure, coinciding with peak abundance of rhythmic basement membrane proteins, were uncovered. This provided multiomic evidence for interactions between glomerular matrix and intracellular time-keeping mechanisms. Furthermore, glucocorticoids, which are frequently used to treat glomerular disease, reset the podocyte clock and induce rhythmic expression of potential glomerular disease genes associated with nephrotic syndrome that included Nphs1 (nephrin) and Nphs2 (podocin). Disruption of the clock with pharmacological inhibition altered the expression of these disease genes, indicating an interplay between clock gene expression and key genes required for podocyte health. Thus, our results provide a strong basis for future investigations of the functional implications and therapeutic potential of chronotherapy in glomerular health and disease. (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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