Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages
Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequen...
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MDPI AG
2024-02-01
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/534 |
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| author | Shao-Chun Wu Cheng-Shyuan Rau Yi-Chan Wu Chia-Jung Wu Chia-Wen Tsai Lien-Hung Huang Chia-Wei Lin Tsu-Hsiang Lu Ming-Yu Yang Ching-Hua Hsieh |
| author_facet | Shao-Chun Wu Cheng-Shyuan Rau Yi-Chan Wu Chia-Jung Wu Chia-Wen Tsai Lien-Hung Huang Chia-Wei Lin Tsu-Hsiang Lu Ming-Yu Yang Ching-Hua Hsieh |
| author_sort | Shao-Chun Wu |
| collection | DOAJ |
| description | Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study’s findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis. |
| first_indexed | 2024-04-24T18:31:50Z |
| format | Article |
| id | doaj.art-fe0fb799a3854657922ad036c2840436 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-24T18:31:50Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-fe0fb799a3854657922ad036c28404362024-03-27T13:22:43ZengMDPI AGBiomedicines2227-90592024-02-0112353410.3390/biomedicines12030534Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in MacrophagesShao-Chun Wu0Cheng-Shyuan Rau1Yi-Chan Wu2Chia-Jung Wu3Chia-Wen Tsai4Lien-Hung Huang5Chia-Wei Lin6Tsu-Hsiang Lu7Ming-Yu Yang8Ching-Hua Hsieh9Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanGraduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanGraduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanCirculating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study’s findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.https://www.mdpi.com/2227-9059/12/3/534sepsisexosomenuclear factor-kappa B (NF-κB)long non-coding RNA (lncRNA)miR-17-92a-1 cluster host gene (MIR17HG)pull-down assay |
| spellingShingle | Shao-Chun Wu Cheng-Shyuan Rau Yi-Chan Wu Chia-Jung Wu Chia-Wen Tsai Lien-Hung Huang Chia-Wei Lin Tsu-Hsiang Lu Ming-Yu Yang Ching-Hua Hsieh Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages Biomedicines sepsis exosome nuclear factor-kappa B (NF-κB) long non-coding RNA (lncRNA) miR-17-92a-1 cluster host gene (MIR17HG) pull-down assay |
| title | Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages |
| title_full | Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages |
| title_fullStr | Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages |
| title_full_unstemmed | Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages |
| title_short | Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages |
| title_sort | circulating exosomes from septic mice activate nf κb mir17hg pathway in macrophages |
| topic | sepsis exosome nuclear factor-kappa B (NF-κB) long non-coding RNA (lncRNA) miR-17-92a-1 cluster host gene (MIR17HG) pull-down assay |
| url | https://www.mdpi.com/2227-9059/12/3/534 |
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