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dc.contributor.authorEtzrodt, Valerie
dc.contributor.authorIdowu, Temitayo O
dc.contributor.authorSchenk, Heiko
dc.contributor.authorSeeliger, Benjamin
dc.contributor.authorPrasse, Antje
dc.contributor.authorThamm, Kristina
dc.contributor.authorPape, Thorben
dc.contributor.authorMüller-Deile, Janina
dc.contributor.authorvan Meurs, Matijs
dc.contributor.authorThum, Thomas
dc.contributor.authorGarg, Ankita
dc.contributor.authorGeffers, Robert
dc.contributor.authorStahl, Klaus
dc.contributor.authorParikh, Samir M
dc.contributor.authorHaller, Hermann
dc.contributor.authorDavid, Sascha
dc.date.accessioned2021-06-03T11:59:53Z
dc.date.available2021-06-03T11:59:53Z
dc.date.issued2021-02-22
dc.identifier.citationCrit Care. 2021 Feb 22;25(1):76. doi: 10.1186/s13054-021-03500-0.en_US
dc.identifier.pmid33618730
dc.identifier.doi10.1186/s13054-021-03500-0
dc.identifier.urihttp://hdl.handle.net/10033/622892
dc.description.abstractBackground: Capillary leakage is a key contributor to the pathological host response to infections. The underlying mechanisms remain incompletely understood, and the role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly in the endothelium thereby contributing to vascular leakage. Methods: SmallRNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs) was done to detect regulated vascular MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease models: LPS 17.5 mg/kgBW and cecal ligation and puncture (CLP); in vitro models: stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance. Results: Endothelial MIR155 was identified as a promising candidate in endotoxemic murine pulmonary ECs (25 × upregulation). Experimental overexpression in a transgenic zebrafish line and in HUVECs was sufficient to induce spontaneous vascular leakage. To the contrary, genetic MIR155 reduction protects against permeability both in vitro and in endotoxemia in vivo in MIR155 heterozygote knockout mice thereby improving survival by 40%. A tight junction protein, Claudin-1, was down-regulated both in endotoxemia and by experimental MIR155 overexpression. Translationally, MIR155 was detectable at high levels in bronchoalveolar fluid of patients with ARDS compared to healthy human subjects. Conclusions: We found that MIR155 is upregulated in the endothelium in mouse and men as part of a systemic inflammatory response and might contribute to the pathophysiology of vascular leakage in a Claudin-1-dependent manner. Future studies have to clarify whether MIR155 could be a potential therapeutic target.en_US
dc.language.isoenen_US
dc.publisherBMCen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectEndotheliumen_US
dc.subjectMicroRNAsen_US
dc.subjectRespiratory distress syndromeen_US
dc.subjectSepsisen_US
dc.subjectTight junctionsen_US
dc.titleRole of endothelial microRNA 155 on capillary leakage in systemic inflammation.en_US
dc.typeArticleen_US
dc.identifier.eissn1466-609X
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalCritical care (London, England)en_US
dc.source.volume25
dc.source.issue1
dc.source.beginpage76
dc.source.endpage
refterms.dateFOA2021-06-03T11:59:53Z
dc.source.journaltitleCritical care (London, England)
dc.source.countryEngland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International