Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bulk RNAseq of ex vivo salt treated isolated human monocytes

ABSTRACT: Salt sensitivity of blood pressure (SSBP) is associated with persistent immune activation after sodium normalization, suggesting immune “salt memory.” Prior work identified that sodium entry into antigen-presenting cells (APCs) via epithelial sodium channels triggers NLRP3 inflammasome activation through the formation of isolevuglandins (IsoLGs), highly reactive lipid aldehydes. IsoLG scavenging with 2-hydroxybenzylamine (2-HOBA) reduces NLRP3 expression and attenuates salt-induced hypertension, implicating IsoLGs as upstream immune regulators. This study tested whether IsoLGs also act as epigenetic modifiers by covalently modifying histone H1, thereby altering chromatin accessibility at inflammatory loci such as NLRP3. PBMCs from 10 hypertensive adults classified as salt-sensitive (SS) or salt-resistant (SR) were collected at baseline, after salt loading, and after depletion. Integrated single-cell RNA-seq and ATAC-seq revealed that SS monocytes exhibited salt-induced enhancer activation and increased chromatin accessibility at the NLRP3 locus. IsoLG–protein adducts correlated with blood pressure changes and were most prominent in CD14⁺ monocytes. In murine APCs, high salt induced IsoLG adduction of histone H1, attenuated by 2-HOBA. Knockdown of H1F0 reduced high salt–induced NLRP3 expression, supporting a role for H1.0 in transcriptional regulation. These findings identify IsoLG modification of histone H1 as a potential mechanism linking extracellular sodium exposure to persistent chromatin remodeling and sustained inflammatory gene expression in SS individuals. IsoLG–histone adducts may represent novel therapeutic targets for immune-driven hypertension.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308365 | GEO | 2025/09/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptomic Analysis in Renal T Lymphocytes Exposes Sodium-Independent Dietary Differences in Dahl Salt-Sensitive Rats

Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.

2019-08-26 | GSE127000 | GEO

Dietary Effects on T Cell Methylomes and Functional Inhibition of DNA Methyltransferase Attenuates Salt-Sensitive Hypertension and Renal Damage in Dahl SS Rat

Project description:The Dahl salt-sensitive (SS) rat is an established model of hypertension and renal damage that is accompanied with an activation of the immune system in the response to a high salt diet. Investigations into the effects of sodium-independent and –dependent components of the diet were shown to affect the disease phenotype with Dahl SS/JrHsdMcwi (SS/MCW) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to the grain-fed Dahl SS/JrHsdMcwiCrl rat (SS/CRL). Recently, T cells isolated from the kidneys of the two strains unveiled that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. Since contributions of the immune system, environment and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these strains. In response to high salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit significantly more differentially methylated regions with a preference for hypermethylation compared to the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between the strains. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. The study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

2019-06-10 | GSE132417 | GEO

Dietary salt and renal function

Project description:Serum and glucocorticoid-induced kinase 1 (SGK1) activates the epithelial sodium channel (eNaC) in tubules. We examined renal SGK1 abundance in salt-adaptation and in salt-sensitive hypertension. Sprague-Dawley and Dahl salt-sensitive rats were placed on either 8% or 0.3% NaCl diets for 10 days. Plasma aldosterone levels were approximately 2.5-fold greater on 0.3% versus 8% NaCl diets in both rat strains. Both serum and glucocorticoid-induced kinase 1 transcript and protein abundance were less (P<0.01) in Sprague-Dawley rats and greater (P<0.01) in Dahl salt-sensitive rats on 8% versus 0.3% NaCl diets. The cDNA sequences of serum and glucocorticoid-induced kinase 1 in both strains of rat were the same. The present results provide evidence that the abundance of serum and glucocorticoid-induced kinase 1 in rat kidney may play a role in salt adaptation and the pathogenesis of hypertension and suggests that aldosterone is not the primary inducer of SGK1 in the Sprague-Dawley rat. Keywords = Rattus norvegicus, Sprague Dawley, Dahl SS/Jr, kidney, NaCl diet Keywords: other

2004-02-14 | GSE599 | GEO

Renal medullary genes in salt-sensitive hypertension

Project description:Substitution of chromosome 13 from Brown Norway BN/SsNHsd/Mcw (BN/Mcw) rats into the Dahl salt-sensitive SS/JrHsd/Mcw (SS/Mcw) rats resulted in substantial reduction of blood pressure salt sensitivity in this consomic rat strain designated SSBN13. In the present study, we attempted to identify genes associated with salt-sensitive hypertension by utilizing a custom, known-gene cDNA microarray to compare the mRNA expression profiles in the renal medulla (a tissue playing a pivotal role in long-term blood pressure regulation) of SS/Mcw and SSBN13 rats on either low-salt (0.4% NaCl) or high-salt (4% NaCl, 2 wk) diets. Keywords: Dahl S rat; blood pressure; kidney; consomic rats

2005-11-17 | GSE3608 | GEO

Effects of potassium supplementation and depletion in the development of salt-sensitive hypertension in male and female rats

Project description:The inverse effects that dietary sodium and potassium have on blood pressure have been known for some time. High sodium consumption is detrimental, while potassium supplementation is known to be beneficial, and the ratio of sodium/potassium consumption is also very important to consider when determining how these electrolytes affect salt-induced hypertension; however, the mechanisms behind the beneficial effects of potassium are still not yet entirely established. Inwardly rectifying potassium (Kir) channels have been shown to play a major role in potassium transport and homeostasis in the kidney and might contribute to these effects. Here we aimed to examine how different variations in the sodium/potassium ratio affect the development of salt-sensitive hypertension and how channels and transporters in the kidney are altered to accommodate these changes. We hypothesize that these diets will affect the development of salt-sensitive hypertension, and that Kir channels will play a major role in the renal adaptations to varying intakes of potassium

2024-02-24 | GSE255582 | GEO

Identification of primate renal salt-responsive gene networks that differ by blood pressure phenotype

Project description:Sodium-lithium countertransport activity (SLC) is an intermediate phenotype for salt sensitive hypertension; elevated SLC corresponds to increased risk of hypertension. Genetic epidemiology studies indicate that SLC is heritable in humans and nonhuman primates; however, little is known about genetic determinants explaining variation in SLC. In this study we identified dietary salt-responsive gene networks in baboon kidneys and salt-responsive networks that differ between baboons with normal and high blood pressure phenotypes.

2018-12-31 | GSE18484 | GEO

Arhgef11 high and low salt kidney proteomic analysis

Project description:Arhgef11 is a Rho guanine nucleotide exchange factor previously implicated in kidney injury in the Dahl salt-sensitive rat (SS-WT). Through exchange of GDP for GTP, Arhgef11 regulates cytoskeletal structure, function, and cell-cell contacts through a variety of stimuli (e.g., G-protein coupled receptors, growth factors, and shear stress). We studied the SS-Arhgef11-/- rat model at 4-12 weeks of age under low and high salt (0.3% or 2% NaCl). To better understand the molecular mechanisms associated with renal protection from loss of Arhgef11, MS/MS proteomics was performed on kidney from SS-Arhgef11-/- and SS-WT at week 12 (low-salt). At week 12, 1017 genes and 363 proteins were observed. In summary, in vivo phenotyping provides strong evidence that increased Arhgef11 expression in the Dahl S rat leads to actin cytoskeleton mediated changes in cell morphology and cell function (impaired reuptake filtered protein) that promote kidney injury, hypertension, and decline in kidney function.

2021-09-08 | PXD011758 | Pride

DNA de novo (de)Methylation in the Kidney Contributes to Salt-Induced Hypertension [RRBS-seq]

Project description:Numerous adult diseases involving tissues that consist primarily of non-dividing cells are associated with changes in DNA methylation. It suggests a role for de novo methylation or demethylation of DNA, which is catalyzed by DNA methyltransferase 3 (Dnmt3) and ten-eleven translocases (Tet). However, the contribution of DNA de novo (de)methylation to these diseases remains nearly completely unproven. Broad changes in DNA methylation occurred within days in the renal outer medulla of Dahl SS rats fed a high-salt diet, a classic model of hypertension. Intra-renal administration of anti-Dnmt3a/Tet3 GapmeR’s attenuated high salt-induced hypertension in SS rats. The high salt diet induced differential expression of 1,712 genes in the renal outer medulla. Remarkably, the differential expression of 76% of these genes were prevented by anti-Dnmt3a/Tet3 GapmeR’s. The genes differentially expressed in response to the GapmeR’s were involved in the regulation of metabolism and inflammation and were significantly enriched for genes showing differential methylation in response to the GapmeR’s. These data indicate DNA de novo (de)methylation in the kidney contributes to the development of hypertension in SS rats. The findings should help to shift the paradigm of DNA methylation research in diseases involving non-dividing cells from correlative analysis to functional and mechanistic studies.

2019-02-13 | GSE114333 | GEO

DNA de novo (de)Methylation in the Kidney Contributes to Salt-Induced Hypertension [RNA-seq]

2019-02-13 | GSE114334 | GEO

Insights into Dahl salt-sensitive hypertension revealed

Project description:The results of this study identified a number of pathways potentially important for the amelioration of hypertension and renal injury in SS-13BN/Mcw rats, and these results generated a series of testable hypotheses related to the role of the renal medulla in the complex mechanism of salt-sensitive hypertension. Keywords: time course, microarray; 11ß-hydroxysteroid dehydrogenase; glucagon receptor; extracellular matrix; apoptosis

2005-11-17 | GSE3588 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data