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Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

ABSTRACT: Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

PROVIDER: PRJNA1125379 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29454034_1.fastq.gz	Fastqsanger.gz
	SRR29454034_2.fastq.gz	Fastqsanger.gz
	SRR29454035_1.fastq.gz	Fastqsanger.gz
	SRR29454035_2.fastq.gz	Fastqsanger.gz
	SRR29454036_1.fastq.gz	Fastqsanger.gz

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Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

Project description:Background: Despite endothelial dysfunction being considered as the initial step of the development of hypertension and associated cardio-renal syndromes, effective therapeutic strategies to prevent endothelial injuries are still lacking. GPR183 is a recently identified GPCR for oxysterols and hydroxylated metabolites of cholesterol. Here, we explored a previously unappreciated role of GPR183 in hypertension and age-related cardio-renal injuries. Methods and results: Mice were treated with DOCA/Salt or AngII to induce hypertension. we found that endothelial GPR183 was significantly induced in aged or hypertensive mice, which was further confirmed in renal biopsies from elderly people or subjects with hypertensive nephropathy. In addition, we found that endothelial-specific GPR183 deletion markedly ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Mechanistically, we found that GPR183 disrupted circadian signaling by inhibiting PER1 expression, thereby facilitating endothelial senescence and dysfunction through the cAMP/PKA/CREB signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or Clotrimazole ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Conclusions: GPR183 is an attractive therapeutic target for hypertension and age-related diseases. Targeting GPR183 could provide novel strategies for managing hypertension and its associated cardio-renal injuries.

2024-06-23 | GSE270175 | GEO

Analysis of mixed-oxysterol treatment on the THP-1 macrophage

Project description:THP-1 monocytes were differentiated, via PMA treatment, to macrophages. THP-1 macrophages were then treated with a mixed-oxysterol treatment (7-ketocholesterol and 7beta-hydroxycholesterol) for 24 hours. The mixed-oxysterol treatment was mixed to a ratio that represents the cytotoxic oxysterol content of human atherosclerotic plaque. Control and treated macrophages were analysed using both 2-DE with peptide mass-fingerprinting and tandem-mass spectrometry.

2017-03-15 | PXD004304 | Pride

Expression of oxysterol pathway genes in estrogen positive breast carcinomas-second phase

Project description:Metabolism of anticancer drugs markedly affects their antitumor effects. The major goal of our study was to investigate associations of gene expression of enzymes metabolizing taxanes and/or anthracyclines with therapy response and survival of breast carcinoma patients The present study investigated transcript levels of key modulators of oxysterol signaling pathway, including oxysterol receptors, metabolic enzymes and transporters in the group of hormone-receptor positive breast carcinoma patients to evaluated potential clinical significance of these genes.

2017-04-06 | GSE85206 | GEO

Expression of oxysterol pathway genes in estrogen positive breast carcinomas-first phase

Project description:Metabolism of anticancer drugs markedly affects their antitumor effects. The major goal of our study was to investigate associations of gene expression of enzymes metabolizing taxanes and/or anthracyclines with therapy response and survival of breast carcinoma patients The present study investigated differences in transcript levels of key modulators of oxysterol signaling pathway, including oxysterol receptors, metabolic enzymes and transporters in the groups of estrogen receptor positive (ER+) breast carcinomas in comparison to estrogen receptor negative (ER-) ones, and to control non-tumor tissues.

2017-04-06 | GSE85207 | GEO

BCOR-regulated genes in human oculo-facio-cardio-dental syndrome

Project description:Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs.

2009-07-23 | GSE15214 | GEO

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

Project description:The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy. Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice.

2012-03-19 | GSE36591 | GEO

BCOR-regulated genes in human oculo-facio-cardio-dental syndrome

2009-07-23 | E-GEOD-15214 | biostudies-arrayexpress

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

2012-03-19 | E-GEOD-36591 | biostudies-arrayexpress

Identifying Non-Invasive Molecular Correlates relevant to Irradiation-Skin Burn Combined Injuries

Project description:Currently there is growing concern with respect to scenarios where people are likely to be presented with radiation exposure along with many kinds of other injuries such as trauma and infection. The potential for such scenarios was brought to reality with the events and aftermath of the Fukushima nuclear disaster in Japan. As such medical complications arising from such exposures would be poorly dealt with as no evidence-based guidelines exist for their rehabilitation or recovery. Our research intends to differentially characterize combined radiation and burn injuries and identify novel pathways and biomarkers. Such findings will lead to better medical practices in the diagnosis, care and rehabilitation of affected individuals. The study includes four groups of mice: 1) Control sham mice group (n=4), 2) Skin burn injury mice group (n=6), 3) Radiation injury mice group (n=6), 4) Combined radiation and burn injury mice group (n=6). We propose to characterize the effects of combined radiation and burn injuries using microRNA microarray analysis. Our primary aim is to identify novel molecular pathways and biomarkers specific to whole blood samples (serum) from mice exposed to combined radiation and burn injuries. B6D2F1/J female mice will be used. 30 days following combined radiation and burn injuries arterial blood will be harvested from euthanized mice. 200ul of serum from whole blood samples will be used for microRNA microarray experiments (Affymetrix).

2015-05-15 | E-GEOD-66739 | biostudies-arrayexpress

Tissue-specific RNA-seq in human evoked inflammation identifies novel blood and adipose lincRNA signatures of cardio-metabolic diseases

Project description:Inappropriate or sustained activation of innate immunity is a pathologic feature of several common cardio-metabolic disorders. Little is known, however, about transcriptomic modulation during inflammatory stress in disease-relevant human tissues. We applied deep RNA sequencing (RNA-seq) during low-dose experimental endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner, inflammatory tissue-level transcriptome responses of relevance to complex cardio-metabolic diseases. We utilized adipose and blood samples from three individuals who underwent a standardized inpatient endotoxemia protocol. Our comprehensive analysis revealed substantial, highly tissue- and subject-specific LPS-modulated changes in the expression of protein-coding genes and linc-RNAs as well as alternative splicing (AS). We also confirmed adipocytes and macrophages as potential cell sources of selective LPS-modulated linc-RNAs and AS events. Finally, we defined disease relevance of a subset of findings in obese adipose tissue and through interrogation of overlap with genome-wide association study loci for cardio-metabolic traits. Our findings provide novel insights into tissue-level genomic regulation, not detectable through analysis of DNA variations alone, of relevance to common cardio-metabolic diseases. Using RNA-seq data to study LPS-modulated changes in lincRNA expression for adipose and blood of a healthy individual.

2014-01-02 | E-GEOD-50792 | biostudies-arrayexpress

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