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Series GSE147243 Query DataSets for GSE147243
Status Public on Mar 20, 2020
Title Macrophage-derived extracellular vesicles regulate concanavalin A-induced hepatitis by suppressing macrophage cytokine production.
Organism Mus musculus
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Acute liver failure is a clinical syndrome of severe hepatic dysfunction. Immune cells play an important role in the failure. In recent years, the immunoregulatory function of extracellular vesicles (EVs) has been reported; therefore, it is inferred that EVs have some role in an immune mediated liver injury. In this study, we investigated the immunoregulatory function of EVs in a concanavalin A (Con A)-induced liver injury. The mouse model was prepared by a single intravenous administration of 15 mg/kg Con A, in which there was a significant increase in serum EVs number. In in vitro study, the secreted EVs number was also significantly increased in Con A-treated RAW264.7, a mouse macrophage cell line, but not Hepa1-6, a mouse hepatoma cell line. In in vitro EVs treatment study, the EVs from Con A-treated mice serum and Con A-treated RAW264.7 suppressed the inflammatory cytokines production in Con A-stimulated RAW264.7. miRNA sequencing analysis showed that mmu-miR-122-5p and mmu-miR-148a-3p were commonly increased in these EVs and the EVs-treated cells. The enriched pathways in the miRNAs predicted target genes included the inflammatory response pathways. mRNA levels of the target genes in the pathways (mitogen-activated protein kinase, Phosphoinositide 3-kinase/Akt and Rho/Rho associated coiled-coil containing protein kinase pathways) were decreased in the EVs-treated cells. In in vivo RNA interference study, knock down of liver RAB27A, an EVs secretion regulator, significantly exacerbated the Con A-induced liver injury. These data suggest that macrophage-derived EVs play an important role in a Con A-induced liver injury through the immunoregulation.
Overall design miRNA profiles in RAW264.7 cells and extracellular vesicles from mouse serum or RAW264.7 culture supernatant were analyzed with MiSeq system (Illumina).
Contributor(s) Kawata R, Oda S, Yokoi T
Citation(s) 32739513
Submission date Mar 19, 2020
Last update date Aug 19, 2020
Contact name Reo Kawata
Organization name Nagoya university
Department Drug Safety Sciences
Lab Toxicogenimics
Street address 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
City Nagoya
ZIP/Postal code 466-8550
Country Japan
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (16)
GSM4422488 PBS/Con A #1
GSM4422489 PBS/Con A #2
GSM4422490 PBS/Con A #3
BioProject PRJNA613488
SRA SRP253377

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Supplementary file Size Download File type/resource
GSE147243_ALL_RAW264.7_samples_Normalized_read_counts.xlsx 61.4 Kb (ftp)(http) XLSX
GSE147243_EVs_raw_read_count.xlsx 37.3 Kb (ftp)(http) XLSX
GSE147243_RAW264.7_raw_read_count.xlsx 63.9 Kb (ftp)(http) XLSX
GSE147243_RAW_Con_A_EVs_Con_A_vs_PBS_Con_A_Normalized_read_counts.xlsx 35.2 Kb (ftp)(http) XLSX
GSE147243_RAW_EVs_Normalized_read_counts.xlsx 18.1 Kb (ftp)(http) XLSX
GSE147243_Serum_Con_A_EVs_Con_A_vs_PBS_Con_A_Normalized_read_counts.xlsx 35.1 Kb (ftp)(http) XLSX
GSE147243_Serum_EVs_Normalized_read_counts.xlsx 17.3 Kb (ftp)(http) XLSX
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