miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6
| Autor: | Weiwei Jiang, Liyong Pu, Weibing Tang, Yeting Lu, Qing-Feng Ni, Wen-Zhou Ding, Liang-Liang Kong, Lianbao Kong, Guo-Qing Liu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
lcsh:Medicine Gene Expression Pharmacology Monocytes White Blood Cells RNA interference Animal Cells Molecular Cell Biology lcsh:Science Receptor Immune Response Cellular Stress Responses Liver injury Innate Immune System Multidisciplinary Cell Death Chemistry Toll-Like Receptors Animal Models Cell Hypoxia Interleukin-1 Receptor-Associated Kinases Liver Cell Processes Reperfusion Injury Cytokines Epigenetics medicine.symptom Signal transduction Cellular Types Signal Transduction Research Article Immune Cells Immunology Down-Regulation Inflammation Mouse Models Research and Analysis Methods Proinflammatory cytokine Cell Line Immunomodulation Model Organisms In vivo medicine Genetics Animals Hepatic Insufficiency Antibody-Producing Cells TNF Receptor-Associated Factor 6 Blood Cells Biology and life sciences Macrophages lcsh:R Immunity Immunoregulation Cell Biology Molecular Development medicine.disease Mice Inbred C57BL MicroRNAs Apoptosis Immune System lcsh:Q Clinical Immunology Reperfusion injury Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 7, p e101530 (2014) |
| ISSN: | 1932-6203 |
| Popis: | A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor- associated factor 6(TRAF6), in the pathogenesis of liver ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and liver I/R injury in vivo and in vitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a in vivo, protected against liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates liver ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6. |
| Databáze: | OpenAIRE |
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