Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of ApoE in communicating immunometabolic signaling in recipient macrophages via exosomes

ABSTRACT: While ApoE expression by myeloid cells is recognized to control inflammation, whether such benefits can be communicated via extracellular vesicles including exosomes is not known. Through the study of exosomes produced by macrophages derived from the bone marrow of Wildtype (WT-BMDM-exo) and ApoE deficient (EKO-BMDM-exo) mice, we uncover a critical role of ApoE in regulating cell signaling properties. We treated BMDM with EKO-BMDM-exo, WT-BMDM-exo, or PBS and performed gene expression profiling analysis. We found that BMDM treated with EKO-BMDM-exo show reductions in the cholesterol efflux gene Abca1 and the long chain fatty acid transporter Cpt1a. Furthermore, BMDM treated with EKO-BMDM-exo show reduced expressions of genes involved in oxidative stress response, particularly the glutathione peroxidases (Gpx1 & Gpx3) and the selenoproteins (Selenow, Selenom, Selenop, and Selenon). In contrast, treatments of these EKO-BMDM-exo upregulated the expressions of genes reported to drive glycolysis or involved in the glycolytic pathway (Aldh2, Pkm, Cd9, Fth1, Dio2, and Pgd). Taken together, our data unveil a novel property of macrophage ApoE in controlling the immunometabolism-regulatory properties by their secreted exosomes.

ORGANISM(S): Mus musculus

PROVIDER: GSE237730 | GEO | 2024/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effect of ApoE in communicating CD4+ T cell activation and proliferation

Project description:While ApoE expression by myeloid cells is recognized to control inflammation, whether such benefits can be communicated via extracellular vesicles including exosomes is not known. Through the study of exosomes produced by macrophages derived from the bone marrow of Wildtype (WT-BMDM-exo) and ApoE deficient (EKO-BMDM-exo) mice, we uncover a critical role of ApoE in regulating cell signaling properties. We treated splenic CD4+ T cells with EKO-BMDM-exo, WT-BMDM-exo, or PBS and performed gene expression profiling analysis. We found that CD4+ T cells treated with EKO-BMDM-exo show elevations in genes involved in the T-cell receptor complex (Cd3e, Cd247, & Cd4) and Il2rg, a key component of cytokine receptors on CD4+ T cells. Taken together, our data unveil a novel property of macrophage ApoE in controlling adaptive immunity by their secreted exosomes.

2023-08-23 | GSE237731 | GEO

High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [RNA-Seq]

Project description:Hyperglycemia is a recognized risk factor for cardiovascular complications in diabetes. While hyperglycemia is known to cause microRNA dysregulation that contributes to cellular activation, whether it can do so through intercellular communication via extracellular vesicles (EVs) is not known. We investigated whether EVs produced under hyperglycemic conditions could communicate signaling to drive atherosclerosis. We did so by treating Apoe−/−mice with exosomes produced by bone marrow‐derived macrophages (BMDM) exposed to high glucose (BMDM–HG-exo) or control. Repeated infusion of BMDM–HG-exo led to a robust increase in hematopoiesis leading to augmented circulating myeloid cell numbers. Four weeks of BMDM–HG-exo infusions increased atherosclerotic lesion sizes with an accumulation of macrophage and apoptotic cells in the aortic root. Transcriptome-wide analysis of naïve cultured macrophages treated with BMDM–HG-exo showed an upregulation of genes associated with cell proliferation. Furthermore, BMDM–HG-exo reprogramed energy metabolism in recipient macrophages with an upregulation of glycolytic activity. Plasma EVs isolated from human subjects with type II diabetes exerted similar cell signaling when incubated with cultured human macrophages. Lastly, profiling microRNA in BMDM–HG-exo and human diabetic plasma EVs converged on miR-486 as commonly enriched. In conclusion, our findings show that EVs serve to communicate detrimental

2021-08-18 | GSE162961 | GEO

High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [miRNA-Seq]

2021-08-18 | GSE162958 | GEO

Effect of ApoE deficiency on microRNA expression in bone marrow derived macrophages (BMDM)

Project description:ApoE exerts pleiotropic properties in controlling inflammation and myeloid cell activation. We here uncover microRNA regulation as yet another mechanism that ApoE acts upon to control immune cell activity and inflammatory response. We compared the expression of microRNAs in BMDM derived from ApoE-KO (EKO) or WIldtype (WT) mice and identified 78 microRNAs to be differentially expressed between these two groups. Among these microRNAs, we identified miR-146a-5p to be highly upregulated in WT BMDM as compared to EKO BMDM. This is consistent with our prior study that reports a role of ApoE in promoting the biogenesis of this microRNA via the transcription of its host gene PU.1 (Spi1) in monocytes/macrophages. Of note, miR-146a-5p is recognized as a potent inhibitor of the NF-κB signaling pathway via the inactivation of IRAK1 and TRAF6. Furthermore, we identified mIR-142a-3p as downregulated in WT BMDM as compared to EKO BMDM. This microRNA has been reported to control important metabolic functions in myeloid cells by targeting the long chain fatty acid transporter CPT1A, thereby inhibiting fatty acid oxidation. Our data thus uncovers another novel of ApoE in controlling lipid metabolism in myeloid cells by suppressing the expression of miR-142a-3p. Taken together, our data provide a novel framework for the microRNA signatures regulated by ApoE in myeloid cells. Moreover, we uncovered an important mechanism of which ApoE can regulate myeloid cell immunometabolism via the regulation of miR-146a-5p and miR-142a-3p.

2023-08-23 | GSE237727 | GEO

Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo

Project description:Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-kB and TNF-a signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe_x0001_/_x0001_ mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-kB and TNF-a via microRNA cargo delivery.

2020-08-06 | GSE155745 | GEO

Exosomal microRNA sequencing in Tongxinluo pretreated and non-treated MSC-derived exosomes

Project description:In order to investigate the specific mechanisms underlying the cardioprotective effects of Tongxinluo pretreated MSC-derived exosomes (MSCTXL-Exo) in cardiac repair, we performed microRNA sequencing on exosomes secreted from Tongxinluo pretreated MSCs and non-treated MSCs to identify differentially expressed miRNA. We found that 18 miRNAs were identified to be upregulated and 25 miRNAs downregulated (over 2-fold change) in MSCTXL-Exo compared to MSC-Exo.

2022-06-01 | GSE184067 | GEO

Exosomal lncRNA sequencing in Atorvastatin treated and non-treated MSC-derived exosomes

Project description:In order to investigate the molecular mechanisms underlying the further enhancement of Atorvastatin pretreated MSC-derived exosomes (MSCATV-Exo) in cardiac protection, we performed lncRNA sequencing on exosomes secreted from ATV pretreated MSCs and non treated MSCs to identify differentially expressed lncRNA. We found that 450 lncRNAs were identified to be upregulated and 1332 lncRNAs downregulated (over 1.5 fold change) in MSCATV-Exo compared to MSC-Exo.

2019-02-28 | GSE113570 | GEO

BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

Project description:BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) in OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses.Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified in OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic genes in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic genes in osteoclasts. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways.

2022-07-07 | GSE197085 | GEO

Exosomal microRNA sequencing in Nicorandil pretreated and non-treated mesenchymal stem cell-derived exosomes

Project description:To investigate the specific miRNA conducting the cardioprotective effect of Nicorandil pretreated MSC-derived exosomes (MSCNIC-Exo) in cardiac repair, we performed microRNA sequencing on exosomes secreted from nicorandil pretreated MSCs and non-treated MSCs to identify differentially expressed miRNA.

2024-03-20 | GSE229889 | GEO

LPS preconditioning enhances the therapeutic efficacy of MSC-derived exosomes in sepsis by altering miRNA expression profile

Project description:Studies have shown that stimulation of Mesenchymal stem cells (MSCs) with biophysical or biochemical cues could influence the contents and biological activities of subsequent MSC-derived exosomes. However, the underlying mechanisms have not been fully clarified. Here, we pretreated MSCs with lipopolysaccharide (LPS) and evaluated exosomes (LPS-Exo) therapeutic effects in sepsis. Analysis of exosomes activity revealed that LPS-Exo treatment improved sepsis to a greater extent than normal MSCs-derived exosomes (Exo). Further analysis revealed that LPS-Exo exert their protective effects mainly through RNA contents. Thus, we hypothesized that LPS preconditioning enhances the therapeutic efficacy of LPS-Exo in sepsis by altering miRNA expression profile.

2024-05-16 | GSE261810 | 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