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dc.contributor.authorWang, Sheng
dc.contributor.authorYang, Yang
dc.contributor.authorSuen, Andrew
dc.contributor.authorZhu, Jing
dc.contributor.authorWilliams, Brittney
dc.contributor.authorHu, Jiang
dc.contributor.authorChen, Fengqian
dc.contributor.authorKozar, Rosemary
dc.contributor.authorShen, Shiqian
dc.contributor.authorLi, Ziyi
dc.contributor.authorJeyaram, Anjana
dc.contributor.authorJay, Steven M.
dc.contributor.authorZou, Lin
dc.contributor.authorChao, Wei
dc.date.accessioned2021-12-07T19:07:36Z
dc.date.available2021-12-07T19:07:36Z
dc.date.issued2021-11-13
dc.identifier.urihttp://hdl.handle.net/10713/17306
dc.description.abstractExtracellular 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. © 2021 The Author(s)en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.language.isoen_USen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofiScienceen_US
dc.subjectCell biologyen_US
dc.subjectImmunologyen_US
dc.subjectMolecular biologyen_US
dc.titleRole of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsisen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.isci.2021.103441
dc.source.volume24
dc.source.issue12


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