Zinc deficiency primes the lung for ventilator-induced injury

Mechanical 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...

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Tipo de recurso:
Fecha de publicación:
2017
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/27224
Acceso en línea:
https://doi.org/10.1172/jci.insight.86507
https://repository.urosario.edu.co/handle/10336/27224
Palabra clave:
Use of Zinc
Treatment of lung conditions
Lessons from mechanical lung ventilation
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dc.title.spa.fl_str_mv Zinc deficiency primes the lung for ventilator-induced injury
dc.title.TranslatedTitle.spa.fl_str_mv La deficiencia de zinc prepara al pulmón para las lesiones inducidas por el ventilador
title Zinc deficiency primes the lung for ventilator-induced injury
spellingShingle Zinc deficiency primes the lung for ventilator-induced injury
Use of Zinc
Treatment of lung conditions
Lessons from mechanical lung ventilation
title_short Zinc deficiency primes the lung for ventilator-induced injury
title_full Zinc deficiency primes the lung for ventilator-induced injury
title_fullStr Zinc deficiency primes the lung for ventilator-induced injury
title_full_unstemmed Zinc deficiency primes the lung for ventilator-induced injury
title_sort Zinc deficiency primes the lung for ventilator-induced injury
dc.subject.keyword.spa.fl_str_mv Use of Zinc
Treatment of lung conditions
Lessons from mechanical lung ventilation
topic Use of Zinc
Treatment of lung conditions
Lessons from mechanical lung ventilation
description Mechanical 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.
publishDate 2017
dc.date.created.spa.fl_str_mv 2017-06-02
dc.date.accessioned.none.fl_str_mv 2020-08-19T14:41:24Z
dc.date.available.none.fl_str_mv 2020-08-19T14:41:24Z
dc.type.eng.fl_str_mv article
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dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1172/jci.insight.86507
dc.identifier.issn.none.fl_str_mv ISSN: 2379-3708
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/27224
url https://doi.org/10.1172/jci.insight.86507
https://repository.urosario.edu.co/handle/10336/27224
identifier_str_mv ISSN: 2379-3708
dc.language.iso.spa.fl_str_mv eng
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dc.relation.citationIssue.none.fl_str_mv No. 11
dc.relation.citationStartPage.none.fl_str_mv Art.e86507
dc.relation.citationTitle.none.fl_str_mv JCI Insight
dc.relation.citationVolume.none.fl_str_mv Vol. 2
dc.relation.ispartof.spa.fl_str_mv JCI Insight, ISSN 2379-3708, Vol.2, No.11 (June, 2017); 15 pp., Art.e86507
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