Metabolic responses of normal rat kidneys to a high salt intake
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA933229 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23387333_1.fastq.gz | Fastqsanger.gz | |||
| SRR23387333_2.fastq.gz | Fastqsanger.gz | |||
| SRR23387334_1.fastq.gz | Fastqsanger.gz | |||
| SRR23387334_2.fastq.gz | Fastqsanger.gz | |||
| SRR23387335_1.fastq.gz | Fastqsanger.gz |
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Project description:In this study, novel methods were developed, which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague-Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to 4.0% NaCl diet. In addition, targeted mRNA expression analysis of cortical segments was performed. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. A novel finding was the increased expression of glycolysis-related genes in Cx and isolated proximal tubular segments in response to an HS diet, consistent with increased release of pyruvate and lactate from the kidney to the renal venous blood. Data suggests that aerobic glycolysis (eg, Warburg effect) may contribute to energy production under these circumstances. The study provides evidence that kidney metabolism responds to an HS diet enabling enhanced energy production while protecting from oxidative stress and injury. Metabolomic and transcriptomic analysis of kidneys of Sprague-Dawley rats fed a high salt diet.
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Project description:Determine changes in the Sprague-Dawley rats' kidney cortex (Cx) and outer medulla (OM) tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to a 4.0% NaCl diet.
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Project description:Rationale— Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding clinical signs or symptoms. It is desirable to prevent AD before the onset. Although high salt intake is an established risk factor for cardiovascular diseases, the relationship between high salt intake and AD has not been clarified. Although recent studies have shown that high salt intake promotes interleukin (IL)-17-dependent inflammation, it is unknown whether this mechanism is involved in the pathogenesis of AD. Objective— The purpose of this study was to investigate the effect of high salt challenge on AD and involvement of IL-17. Methods and Results— We used a mouse AD model that was induced by continuous infusion of -aminopropionitrile and angiotensin II. High salt challenge exacerbated AD lesion length compared to the mice without high salt challenge, which was abolished in IL-17 knockout mice. Unexpectedly, deletion of IL-17 resulted in the activation of Smad pathway, induction of synthetic phenotype of smooth muscle cells, remodeling of extracellular matrix in aortic tunica media, reduced stiffness of aortic walls, and less stress-induced activation of NFkB. Conclusions— These findings establish the worsening effect of high salt intake on AD that involves IL-17 pathway through the extracellular matrix metabolism. Salt restriction may represent a low-cost and practical way to reduce AD risk.
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Project description:Dahl-Iwai (DI) salt-sensitive rats were studied using microarrays to identify gender-specific differences in the kidney, both basal differences and responses to a high salt diet. In DI rat kidneys, gene expression profiles demonstrated inflammatory and fibrotic responses selectively in females. Gonadectomy of DI rats abrogated gender differences in gene expression. Gonadectomized female and gonadectomized male DI rats both responded to high salt with the same spectrum of gene expression changes as intact female DI rats. Androgens dominated the gender selective responses to salt. Several androgen-responsive genes were identified with roles potentiating the differential responses to salt including increased male expression of Angiotensin-Vasopressin Receptor and Prolactin Receptor, decreased 5-alpha reductase, and mixed increases and decreases in expression of Cyp4a- genes that can produce eicosanoid hormones. These gender differences potentiate sodium retention by males, and increase kidney function during gestation by females. Experiment Overall Design: - 68 samples/rats/data tables are represented. Experiment Overall Design: - One microarray was used for each sample. Experiment Overall Design: - 3 rat
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