Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human seps...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221014127 |
| _version_ | 1819174666544087040 |
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| author | Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao |
| author_facet | Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao |
| author_sort | Sheng Wang |
| collection | DOAJ |
| description | Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis. |
| first_indexed | 2024-12-22T20:42:36Z |
| format | Article |
| id | doaj.art-ecd205c2503c41b38a4ba374510447a3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-22T20:42:36Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ecd205c2503c41b38a4ba374510447a32022-12-21T18:13:18ZengElsevieriScience2589-00422021-12-012412103441Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsisSheng Wang0Yang Yang1Andrew Suen2Jing Zhu3Brittney Williams4Jiang Hu5Fengqian Chen6Rosemary Kozar7Shiqian Shen8Ziyi Li9Anjana Jeyaram10Steven M. Jay11Lin Zou12Wei Chao13Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Diagnostic Ultrasound, The Second Xiangya Hospital, Central South University, Changsha, ChinaCenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, NS, CanadaCenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USAProgram in Trauma & Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USADepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USADepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAFischell Department of Bioengineering, A James Clark School of Engineering, University of Maryland, College Park, MD 20742, USAFischell Department of Bioengineering, A James Clark School of Engineering, University of Maryland, College Park, MD 20742, USACenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding authorCenter for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding authorSummary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis.http://www.sciencedirect.com/science/article/pii/S2589004221014127Molecular biologyImmunologyCell biology |
| spellingShingle | Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis iScience Molecular biology Immunology Cell biology |
| title | Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis |
| title_full | Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis |
| title_fullStr | Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis |
| title_full_unstemmed | Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis |
| title_short | Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis |
| title_sort | role of extracellular microrna 146a 5p in host innate immunity and bacterial sepsis |
| topic | Molecular biology Immunology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221014127 |
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