Similar Datasets
Project description:Effect of LXR ligands on gene expression in human PDAC cells
| PRJNA910541 | ENA
Project description:The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways, including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand the knowledge of the functions of LXR signaling during embryonic development, we performed a whole-genome microarray analysis of Lxr target genes in zebrafish larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965. Assessment of the biological processes enriched by differentially expressed genes revealed a prime role for Lxr in regulating lipid metabolic processes, similarly to the function of LXR in mammals. In addition, exposure to the Lxr ligands induced changes in expression of genes in the neural retina and lens of the zebrafish eye, including the photoreceptor guanylate cyclase activators and lens gamma crystallins, suggesting a potential novel role for Lxr in modulating the transcription of genes associated with visual function in zebrafish. The regulation of expression of metabolic genes was phenotypically reflected in an increased absorption of yolk in the zebrafish larvae, and changes in the expression of genes involved in visual perception were associated with morphological alterations in the retina and lens of the developing zebrafish eye. The regulation of expression of both lipid metabolic and eye specific genes was sustained in 1 month old fish. The transcriptional networks demonstrated several conserved effects of LXR activation between zebrafish and mammals, and also identified potential novel functions of Lxr, supporting zebrafish as a promising model for investigating the role of Lxr during development.
2016-03-07 | GSE59031 | GEO
Project description:Dysregulation of cholesterol metabolism and homeostasis is associated with the pathology of many diseases such as cardiovascular disease and cancer. Two major upstream regulators of cholesterol homeostasis are the SREBP2 pathway and the actions of the liver X receptors (LXRs), with the liver thought to handle the majority of cholesterol homeostasis at the organismal level. Endogenous cholesterol metabolites such as 27-hydroxycholesterol (27HC), which serve to activate the nuclear receptor LXR, result in increased expression of genes associated with cholesterol catabolism and efflux. LXR and various LXR ligands such as 27HC have been described to influence several extra-hepatic biological systems. However, disparate reports of LXR function have emerged, especially with respect to immunology and cancer biology. This would suggest that similar to steroid nuclear receptors, the LXR may be selectively modulated by ligands. Here, we use bulk RNA-sequencing of bone marrow-derived macrophages and single-cell RNA-sequencing of immune cells from murine lungs bearing metastatic mammary cancer, to prove that LXR satisfies the two principles of selective nuclear receptor modulation: (1) different LXR ligands result in overlapping but distinct gene expression profiles within the same cell type, and (2) the same LXR ligands differentially regulate gene expression in a highly context-specific manner, depending on cell or tissue type. The concept that the LXR can be selectively modulated provides the foundation for the development of ligands that are tailored to promote those activities that are desirable (pro-immune), but at the same time minimizing harmful side effects (such as elevated triglyceride levels).
2022-06-01 | GSE186910 | GEO
Project description:Dysregulation of cholesterol metabolism and homeostasis is associated with the pathology of many diseases such as cardiovascular disease and cancer. Two major upstream regulators of cholesterol homeostasis are the SREBP2 pathway and the actions of the liver X receptors (LXRs), with the liver thought to handle the majority of cholesterol homeostasis at the organismal level. Endogenous cholesterol metabolites such as 27-hydroxycholesterol (27HC), which serve to activate the nuclear receptor LXR, result in increased expression of genes associated with cholesterol catabolism and efflux. LXR and various LXR ligands such as 27HC have been described to influence several extra-hepatic biological systems. However, disparate reports of LXR function have emerged, especially with respect to immunology and cancer biology. This would suggest that similar to steroid nuclear receptors, the LXR may be selectively modulated by ligands. Here, we use bulk RNA-sequencing of bone marrow-derived macrophages and single-cell RNA-sequencing of immune cells from murine lungs bearing metastatic mammary cancer, to prove that LXR satisfies the two principles of selective nuclear receptor modulation: (1) different LXR ligands result in overlapping but distinct gene expression profiles within the same cell type, and (2) the same LXR ligands differentially regulate gene expression in a highly context-specific manner, depending on cell or tissue type. The concept that the LXR can be selectively modulated provides the foundation for the development of ligands that are tailored to promote those activities that are desirable (pro-immune), but at the same time minimizing harmful side effects (such as elevated triglyceride levels).
2022-06-01 | GSE186909 | GEO
Project description:The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.
2012-09-29 | GSE41223 | GEO
Project description:This microarray is an analysis of differentially expressed genes in three pancreatic ductal adenocarcinoma cell lines treated with LXR-agonist GW 3965. We first report that GW 3965 has antiproliferative effects in three PDAC cell lines. This microarray was designed to identify key mechanisms of the antiproliferative effect of LXR agonists within pancreatic cancer cell lines. Total RNA obtained from BxPC-3, MIA-PaCa-2, and PANC-1 pancreatic cancer cells grown in culture treated GW 3965 or ethanol (vehicle control) for 72 hours.
2014-04-15 | E-GEOD-51656 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. Here we report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL‑36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb.
2018-02-14 | GSE103092 | GEO
Project description:Dendritic cells (DCs) play a crucial role in the regulation of innate and adaptive immune responses. DCs initiate adaptive immune responses after their migration to secondary lymphoid organs, a process mainly driven by the expression of the chemokine receptor CCR7. LXR ligands/oxysterols released by tumors were shown to dampen DC migration to secondary lymphoid organs by the inhibition of CCR7 expression. We studied the gene expression modulation of DCs undergoing maturation (by LPS) in the presence of the oxysterol 22R-Hydroxycholesterol (22R-HC).
2019-02-27 | E-MTAB-6224 | biostudies-arrayexpress
Project description:To identify novel LXR target genes, we conducted transcriptional profiling studies using RAW264.7 cells ectopically expressing LXRalpha
2009-08-01 | GSE17088 | GEO
Project description:The project is based on the transcriptomic analysis from 8 groups of animal samples : Wild Type Sham Wild Type Castrated LXR-/- Sham LXR-/- Castrated PTEN-/- Sham PTEN-/- Castrated PTEN-/-LXR-/- Sham PTEN-/-LXR-/- Castrated.
2020-07-31 | GSE134137 | GEO