Extracellular vesicles from hepatocytes are therapeutic for toxin-mediated fibrosis and gene expression in the liver
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE136152 | GEO | 2019/12/18
REPOSITORIES: GEO
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Project description:We studied transcriptomic changes of extracellular vesicles (EVs) in bronchoalveolar lavage fluid of bleomycin-injured wild-type and syndecan-1 deficient mice
2019-07-27 | GSE134948 | GEO
Project description:Compared to whole serum miRNAs, miRNAs in serum small extracellular vesicles (sEVs) are well protected form RNA enzymes, thus provide a consistent source of miRNA for disease biomarker detection. Serum sEVs and their miRNA cargos released by injured liver cells could be promising biomarkers for diagnosis of liver diseases. We were very interested to find out the effects of liver injury on serum extracellular vesicles as well as the small RNA components they transported, if there is any difference between acute and chronic injury. Study in this regard will help us to identify new serum biomarkers for liver injury, and to find out if there are specific markers for acute or chronic liver injury. To identify potential biomarker for liver injury based on serum sEVs miRNAs, we established the carbon tetrachloride (CCL4) induced acute and chronic liver injury mice model, and examined the dynamic changes of small RNA components, especially miRNAs, in serum sEVs.
2021-08-07 | E-MTAB-9462 | biostudies-arrayexpress
Project description:We evaluted the effects of extracellular vesicles of bleomycin-injured wild-type and syndecan-1 deficient mice on mouse lung epithelial cell line (MLE-12) total transcriptomic changes (bulk mRNA sequencing)
2019-07-24 | GSE134741 | GEO
Project description:Extracellular vesicles (EVs) are nano-sized membrane-limited organelles that are liberated from their producer cells, traverse the intercellular space, and may interact with other cells resulting in the uptake of the EV molecular payload by the recipient cells which may become functionally reprogramed as a result. Previous in vitro studies showed that EVs purified from normal mouse AML12 hepatocytes ("EVNorm") attenuate the pro-fibrogenic activities of activated hepatic stellate cells (HSCs), a principal fibrosis-producing cell type in the liver. In a 10-day CCl4 injury model, liver fibrogenesis, expression of hepatic cellular communication network factor 2 [CCN2, also known as connective tissue growth factor (CTGF)] or alpha smooth muscle actin (αSMA) was dose-dependently blocked during concurrent administration of EVNorm. Hepatic inflammation and expression of inflammatory cytokines were also reduced by EVNorm. In a 5-week CCl4 fibrosis model in mice, interstitial collagen deposition and mRNA and/or protein for collagen 1a1, αSMA or CCN2 were suppressed following administration of EVNorm over the last 2 weeks. RNA sequencing (RNA-seq) revealed that EVNorm therapy of mice receiving CCl4 for 5 weeks resulted in significant differences [false discovery rate (FDR) <0.05] in expression of 233 CCl4-regulated hepatic genes and these were principally associated with fibrosis, cell cycle, cell division, signal transduction, extracellular matrix (ECM), heat shock, cytochromes, drug detoxification, adaptive immunity, and membrane trafficking. Selected gene candidates from these groups were verified by qRT-PCR as targets of EVNorm in CCl4-injured livers. Additionally, EVNorm administration resulted in reduced activation of p53, a predicted upstream regulator of 40% of the genes for which expression was altered by EVNorm following CCl4 liver injury. In vitro, EVs from human HepG2 hepatocytes suppressed fibrogenic gene expression in activated mouse HSC and reversed the reduced viability or proliferation of HepG2 cells or AML12 cells exposed to CCl4. Similarly, EVs produced by primary human hepatocytes (PHH) protected PHH or human LX2 HSC from CCl4-mediated changes in cell number or gene expression in vitro. These findings show that EVs from human or mouse hepatocytes regulate toxin-associated gene expression leading to therapeutic outcomes including suppression of fibrogenesis, hepatocyte damage, and/or inflammation.
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Project description:We then compared whole transcriptome bulk RNA-seq data of dHeps isolated from CCl4-injured mice and treated with either 5C, 3C, or DMSO. The expression of hepatocyte-enriched TFs and hepatocyte functional genes was upregulated in both the 5C and 3C groups, while mesenchymal markers (Acta2, Mmp3), inflammatory-related genes (Cxcl10, Ecm1, Ccl6, and Cd68), and oxidative stress-related genes (Ncf2 and Ncf1), were down-regulated compared with their expression in the DMSO control group
2023-11-21 | GSE233081 | GEO
Project description:Similar to bacterial proteins that are targeted to distinct macrophages organelles via extracellular vesicles, we propose that these vesicles also traffic small RNAs to modulate specific host factors. To test this, we aim to sequence extracellular vesicle derived sRNA, and whole bacterial small RNAs to determine selectivity, and to identify their bacterial and mammalian targets (Experimental Plan in Table-1). For this we will collect highly purified vesicles from N. gonorrhoeae (strain MS11A). We will also treat mouse derived primary macrophages with extracellular vesicles and compare their RNA response to untreated macrophages (Table-2). This will provide novel insights into how macrophages respond to N. gonorrhoeae infections. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2016-03-01 | E-ERAD-439 | biostudies-arrayexpress
Project description:Background: There is some evidence demonstrating the effect of psychological interventions in improvements in health biological parameters. To best of our knowledge, no study had addressed the impact of any psychological intervention on extracellular vesicles. In addition, Mindfulness-Based Cognitive Therapy (MBCT) and Emotion Focused Therapy for Cancer Recovery (EFT-CR) in the group have never been explored regarding extracellular vesicles and the effectiveness of these was not compared yet.
Objectives:
1. To explore and compare the effect of MBCT and EFT-CR on biological parameters and psychological variables in distressed people who have had breast, prostate and colorectal cancer;
2. In addition, we will explore the acceptability through recruitment and retention rates of MBCT and EFT-CR in group and evaluate whether these interventions are appropriate for a larger clinical trial.
Methods: The design of this study is a parallel randomized controlled trial. Participants will be randomized into MBCT, EFT-CR or usual care. Outcome measures will be assessed before, at the end of the intervention (8 weeks) and follow-ups (24 and 52 weeks from the baseline moment).
Hypotheses: The researchers expected that both interventions will have an effect on extracellular vesicles and other study biomarkers as well as improvements in psychological outcomes, compared to treatment as usual (TAU) group. Regarding the comparative effectiveness, we did not have evidence to hypothesize which one of the interventions will be superior in both biological (extracellular vesicles) and psychological outcomes.
Contribution for practice: The results of this preliminary study would permit to know if there are benefits of these psychological interventions on changes in extracellular vesicles and on psychological outcomes related to health. In addition, this study will permit to determine the acceptability of conducting a larger randomized controlled trial.
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