dc.contributor.author | Suen, Andrew Oliver | |
dc.date.accessioned | 2023-04-10T17:01:25Z | |
dc.date.available | 2023-04-10T17:01:25Z | |
dc.date.issued | 2023-02-14 | |
dc.identifier.uri | http://hdl.handle.net/10222/82361 | |
dc.description.abstract | Inflammatory responses frequently follow severe traumatic injury and are, in part, a consequence of innate immune activation by endogenous immune triggers such as extracellular and micro-(mi)RNAs recognized by the pattern recognition receptor Toll-like receptor 7 (TLR7). However, excessive immune responses may lead to inappropriate systemic inflammation that contributes to multiple organ failure. Here, we developed a novel mouse model of polytraumatic injury and evaluated the circulating plasma RNAs and miRNAs. We report that polytrauma causes significant elevations in plasma miRNA with distinct patterns of up- and down-regulation of host plasma small miRNAs. Next, we tested the pro-inflammatory function of miRNAs in bone marrow-derived macrophage culture and in a murine air pouch model of inflammation. We found that miRNAs with high uridine (U) contents >40% released into circulation induce a robust TLR7-dependent inflammatory response, revealing a pivotal role of circulating U-rich miRNAs as a key damage-associated molecular pattern (DAMP) in polytrauma. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | Trauma | en_US |
dc.subject | Innate Immunity | en_US |
dc.subject | microRNA | en_US |
dc.subject | Extracellular microRNA | en_US |
dc.title | Circulating microRNAs Trigger Innate Immune Activation in Polytraumatic Injury | en_US |
dc.date.defence | 2020-08-12 | |
dc.contributor.department | Medical Research Graduate Program | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | Dr. Eric You-Ten, MD PhD | en_US |
dc.contributor.graduate-coordinator | Dr. Michael Bezuhly | en_US |
dc.contributor.thesis-reader | Dr. Lin Zou, MD PhD | en_US |
dc.contributor.thesis-reader | Dr. Beata Derfalvi, MD PhD | en_US |
dc.contributor.thesis-reader | Dr. Wei Chao, MD PhD | en_US |
dc.contributor.thesis-supervisor | Dr. Christian Lehmann, MD PhD | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |