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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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).
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| 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
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| Department |
Drug Safety Sciences
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| Lab |
Toxicogenimics
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| Street address |
65 Tsurumai-cho, Showa-ku, Nagoya, Japan
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| City |
Nagoya |
| ZIP/Postal code |
466-8550 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA613488 |
| SRA |
SRP253377 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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