RNA sequencing of CD11b+ mouse bone marrow cells in mice treated with exosomes with or without HDL mimicking nanoparticles
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ABSTRACT:
PROVIDER: PRJNA663621 | ENA |
REPOSITORIES: ENA
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Project description:We report the sequencing of total RNA from CD11b+ mouse bone marrow cells in three groups of C57BL/6 mice: 1) Mice treated with three systemic (tail vein) injections (Days 1, 3, and 5) of phosphate buffered saline (PBS) (pH = 7.4), 2) Mice treated with three tail vein injections (Days 1, 3, and 5) of exosomes derived from enzalutamide resistant CWR-R1 prostate cancer cells (EnzR exosomes), and 3) Mice treated with three tail vein injections of EnzR exosomes (Days 1, 3, and 5) and high-density lipoprotein mimetic nanoparticles (HDL NPs) (Days 0, 2, and 4). Mice were sacrificed on Day 6, when mouse bone marrow was harvested and RNA from CD11b+ cells was obtained. We find that mice treated with EnzR exosome exhibit alteration in the expression of the matricellular protein, thrombospondin-1. Moreover, we find that HDL NP pre-treatment prevented thrombospondin-1 downregulation in mice treated with EnzR exosomes. This is consistent with our published findings that HDL NPs inhibit the uptake of EnzR exosomes by CD11b+ mouse bone marrow cells.
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Project description:We report changes in gene expression in the Burkitt's lymphoma cell line Ramos, treated with high density lipoprotein-like nanoparticles (HDL NPs) for 48 hours, compared to saline (NT) and natural, human HDL treatment
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Project description:High-density lipoproteins (HDL) are nanoparticles with >80 associated proteins, phospholipids, cholesterol and cholesteryl esters. We have identified and quantified the ultracentrifugation isolated HDL proteome across 93 strains of mice, a diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP).
2019-04-24 | PXD009473 | Pride
Project description:Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing. Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing. Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing.
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Project description:Exosomes are cell-derived nanovesicles with a proven key role in intercellular signaling, inflammation processes and immune response. Due to their natural origin and liposome-like structure, these nanometric vesicles have emerged as novel platforms for therapy and diagnosis. This work presents goat’s milk exosomes as natural nanoparticles applied in the detection of inflammatory processes by optical imaging. Goat’s milk exosomes were isolated and fully characterized by their physicochemical properties, proteomics profile and biochemical impact in healthy mice. For the in vitro and in vivo assessment, these nanoparticles were covalently labeled with sulfo-Cyanine 5 and BODIPY-FL. In vitro studies confirmed the internalization of the nanoprobe as well as no cytotoxicity in macrophages populations (RAW 264.7). The capacity of our probe to localize inflammatory processes was in vivo assessed by optical imaging in a peritonitis mouse model confirmed. These results were also confirmed by the flow cytometry analysis of the peritonitis exudates, supporting the use of these natural nanoparticles in the detection of inflammatory processes.
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Project description:miRNAs and other small RNAs have been found associated with high-density lipoproteins (HDL). The aim of this study was to investigate the miRNA signature on human HDL from 10 donors.
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Project description:We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control. These data were used to determine which genes are regulated by native HDL compared to components of HDL and categorize data based on shared sets of genes and distinct sets of genes regulated by each component.
2014-02-27 | GSE53201 | GEO
Project description:Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDL’s ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathway’s potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDL’s major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-I–deficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection. 12 arrays, 3 experimental groups, mMncN (no treatment), mMncL (LPS treated, exposed for 4 h to serum-free medium or serum-free medium supplemented with 100 ng/mL of LPS), and mMwtL (HDL treated, Macrophages were treated for 4 h with serum-free medium or serum-free medium supplemented with 50 mg/mL of HDL, washed twice with PBS).
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Project description:miRNAs are exported to high density lipoproteins (HDL). This study aimed to understand what miRNAs are exported from primary islets to HDL in vitro.
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Project description:We quantified differential microRNA (miRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control. These data were used to determine whichmiRNAs are regulated by native HDL compared to components of HDL and categorize data based on shared sets of miRNAs and distinct sets of miRNAs regulated by each component.
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