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Zinc deficiency primes the lung for ventilator-induced injury

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dc.creatorBoudreault, Francisspa
dc.creatorPinilla-Vera,Miguelspa
dc.creatorEnglert, Joshua A.spa
dc.creatorKho,Alvin T.spa
dc.creatorIsabelle, Colleenspa
dc.creatorArciniegas, Antonio J.spa
dc.creatorBarragan-Bradford, Dianaspa
dc.creatorQuintana, Carolinaspa
dc.creatorAmador Muñoz, Diana Patricia
dc.creatorGuan, Jiazhenspa
dc.creatorMoo Choi, Kyoungspa
dc.creatorRegistry, MICUspa
dc.creatorSholl, Lynettespa
dc.creatorHurwitz, Shelleyspa
dc.creatorTschumperlin, Daniel J.spa
dc.creatorBaron, Rebecca M.spa
dc.date.accessioned2020-08-19T14:41:24Z
dc.date.available2020-08-19T14:41:24Z
dc.date.created2017-06-02spa
dc.description.abstractMechanical ventilation is necessary to support patients with acute lung injury, but also exacerbates injury through mechanical stress–activated signaling pathways. We show that stretch applied to cultured human cells, and to mouse lungs in vivo, induces robust expression of metallothionein, a potent antioxidant and cytoprotective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency of murine metallothionein genes exacerbated lung injury caused by high tidal volume mechanical ventilation, identifying an adaptive role for these genes in limiting lung injury. Stretch induction of metallothionein required zinc and the zinc-binding transcription factor MTF1. We further show that mouse dietary zinc deficiency potentiates ventilator-induced lung injury, and that plasma zinc levels are significantly reduced in human patients who go on to develop acute respiratory distress syndrome (ARDS) compared with healthy and non-ARDS intensive care unit (ICU) controls, as well as with other ICU patients without ARDS. Taken together, our findings identify a potentially novel adaptive response of the lung to stretch and a critical role for zinc in defining the lung’s tolerance for mechanical ventilation. These results demonstrate that failure of stretch-adaptive responses play an important role in exacerbating mechanical ventilator–induced lung injury, and identify zinc and metallothionein as targets for lung-protective interventions in patients requiring mechanical ventilation.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1172/jci.insight.86507
dc.identifier.issnISSN: 2379-3708
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/27224
dc.language.isoengspa
dc.publisherAmerican Society for Clinical Investigationspa
dc.relation.citationIssueNo. 11
dc.relation.citationStartPageArt.e86507
dc.relation.citationTitleJCI Insight
dc.relation.citationVolumeVol. 2
dc.relation.ispartofJCI Insight, ISSN 2379-3708, Vol.2, No.11 (June, 2017); 15 pp., Art.e86507spa
dc.relation.urihttps://insight.jci.org/articles/view/86507/pdfspa
dc.relation.urihttp://jci.me/86507-pdfspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.sourceJCI Insightspa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordUse of Zincspa
dc.subject.keywordTreatment of lung conditionsspa
dc.subject.keywordLessons from mechanical lung ventilationspa
dc.titleZinc deficiency primes the lung for ventilator-induced injuryspa
dc.title.TranslatedTitleLa deficiencia de zinc prepara al pulmón para las lesiones inducidas por el ventiladorspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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