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Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock

ABSTRACT: Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock

PROVIDER: PRJNA892713 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21996615.fastq.gz	Fastqsanger.gz
	SRR21996616.fastq.gz	Fastqsanger.gz
	SRR21996617.fastq.gz	Fastqsanger.gz
	SRR21996618.fastq.gz	Fastqsanger.gz
	SRR21996619.fastq.gz	Fastqsanger.gz

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Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock

Project description:Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that ~30% RNAs, ~20% proteins and ~20% metabolites are rhythmic in kidneys of control mice. Several key metabolic pathways including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and b-oxidation displayed impairments in kidneys of cKOt, resulting in a perturbed mitochondrial activity. Carnitine reabsorption from the primary urine was one of the most impacted processes with a ~50% reduction in plasma carnitine levels and a parallel systemic decrease in tissues carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.

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Project description:The activation of hypoxia-inducible transcription factors (HIF) leading to the expression of hundreds of target genes is a fundamental mechanism in acute and chronic kidney disease, mediating protective but possibly harmful effects. Furthermore, dysregulation of the HIF pathway in chronic kidney disease causes renal anemia through insufficient erythropoietin (EPO) induction in interstitial cells. RNA-seq analysis was performed in human primary renal tubular cells to analyse the effect of HIF stabilization on the expression of genes in tubular cells. ATAC-seq and HIF-CHIP-seq complement the data to analyse transcription factor binding and chromatin configuration changes.

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2022-04-22 | GSE119426 | GEO

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