Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles
Summary: Sepsis-associated acute liver injury (SALI) is an independent risk for sepsis-induced death orchestrated by innate and adaptive immune responses. Here, we found that Roquin-1 was decreased during SALI and expressed mainly in monocyte-derived macrophages. Meanwhile, Roquin-1 was correlated w...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422301372X |
| _version_ | 1797770024477261824 |
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| author | Lei Zheng Wei Ling Deming Zhu Zhi Li Yousheng Li Haoming Zhou Lianbao Kong |
| author_facet | Lei Zheng Wei Ling Deming Zhu Zhi Li Yousheng Li Haoming Zhou Lianbao Kong |
| author_sort | Lei Zheng |
| collection | DOAJ |
| description | Summary: Sepsis-associated acute liver injury (SALI) is an independent risk for sepsis-induced death orchestrated by innate and adaptive immune responses. Here, we found that Roquin-1 was decreased during SALI and expressed mainly in monocyte-derived macrophages. Meanwhile, Roquin-1 was correlated with the inflammatory profiles in humans and mice. Mechanically, Roquin-1 in macrophages promoted Ago2-K258-ubiquitination and inhibited Ago2-S387/S828-phosphorylation. Ago2-S387-phosphorylation inhibited Ago2-miRNA’s complex location in multivesicular bodies and sorting in macrophages-derived extracellular vesicles (MDEVs), while Ago2-S828-phosphorylation modulated the binding between Ago2 and miRNAs by special miRNAs-motifs. Then, the anti-inflammatory miRNAs in MDEVs decreased TSC22D2 expression directly, upregulated Tregs-differentiation via TSC22D2-STAT3 signaling, and inhibited M1-macrophage-polarization by TSC22D2-AMPKα-mTOR pathway. Furthermore, WT MDEVs in mice alleviated SALI by increasing Tregs ratio and decreasing M1-macrophage frequency synchronously. Our study showed that Roquin-1 in macrophages increased Tregs-differentiation and decreased M1-macrophage-polarization simultaneously via miRNA in MDEVs, suggesting Roquin-1 can be used as a potential tool for SALI treatment and MDEVs engineering. |
| first_indexed | 2024-03-12T21:17:29Z |
| format | Article |
| id | doaj.art-11049fb896854521a6caba6d9aa56f31 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T21:17:29Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-11049fb896854521a6caba6d9aa56f312023-07-29T04:35:43ZengElsevieriScience2589-00422023-08-01268107295Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesiclesLei Zheng0Wei Ling1Deming Zhu2Zhi Li3Yousheng Li4Haoming Zhou5Lianbao Kong6Hepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. China; Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao-tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, P.R. ChinaHepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. ChinaHepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. ChinaHepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. ChinaDepartment of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao-tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, P.R. China; Corresponding authorHepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. China; Corresponding authorHepatobiliary Center/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. China; Corresponding authorSummary: Sepsis-associated acute liver injury (SALI) is an independent risk for sepsis-induced death orchestrated by innate and adaptive immune responses. Here, we found that Roquin-1 was decreased during SALI and expressed mainly in monocyte-derived macrophages. Meanwhile, Roquin-1 was correlated with the inflammatory profiles in humans and mice. Mechanically, Roquin-1 in macrophages promoted Ago2-K258-ubiquitination and inhibited Ago2-S387/S828-phosphorylation. Ago2-S387-phosphorylation inhibited Ago2-miRNA’s complex location in multivesicular bodies and sorting in macrophages-derived extracellular vesicles (MDEVs), while Ago2-S828-phosphorylation modulated the binding between Ago2 and miRNAs by special miRNAs-motifs. Then, the anti-inflammatory miRNAs in MDEVs decreased TSC22D2 expression directly, upregulated Tregs-differentiation via TSC22D2-STAT3 signaling, and inhibited M1-macrophage-polarization by TSC22D2-AMPKα-mTOR pathway. Furthermore, WT MDEVs in mice alleviated SALI by increasing Tregs ratio and decreasing M1-macrophage frequency synchronously. Our study showed that Roquin-1 in macrophages increased Tregs-differentiation and decreased M1-macrophage-polarization simultaneously via miRNA in MDEVs, suggesting Roquin-1 can be used as a potential tool for SALI treatment and MDEVs engineering.http://www.sciencedirect.com/science/article/pii/S258900422301372XPathophysiologyMolecular biologyImmunology |
| spellingShingle | Lei Zheng Wei Ling Deming Zhu Zhi Li Yousheng Li Haoming Zhou Lianbao Kong Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles iScience Pathophysiology Molecular biology Immunology |
| title | Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles |
| title_full | Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles |
| title_fullStr | Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles |
| title_full_unstemmed | Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles |
| title_short | Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles |
| title_sort | roquin 1 resolves sepsis associated acute liver injury by regulating inflammatory profiles via mirna cargo in extracellular vesicles |
| topic | Pathophysiology Molecular biology Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422301372X |
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