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...
- Autores:
- 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
- Rights
- License
- Abierto (Texto Completo)
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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 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_6501 |
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 |
language |
eng |
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 |
dc.relation.uri.spa.fl_str_mv |
https://insight.jci.org/articles/view/86507/pdf http://jci.me/86507-pdf |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
American Society for Clinical Investigation |
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JCI Insight |
institution |
Universidad del Rosario |
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instname:Universidad del Rosario |
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reponame:Repositorio Institucional EdocUR |
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fe0c600f-e92d-4d69-b02d-7056f74e7287-131fc6727-d320-4c96-b516-05b29af46116-1d1d619eb-097f-4e64-a0bd-563ad802e073-1097c8d23-0b25-4f19-8236-6ffc48fad09d-107b85989-8803-455f-9eb2-b80c2dec6dc8-1b0a157fb-9301-4c67-ba49-2f7e52de3432-1645101bf-78be-4e14-9d9c-91a9b2c4dbc9-193be064a-b107-4085-8244-89dcff48bd6b-184316359-3f90-4b7e-bbda-e4e077df813a-17dab6614-9456-4ad0-bf29-96f0c273bca0-101b64304-bdfc-410b-abb5-a78be36ebca8-1ac66ad97-a019-4de0-b620-ea0b5de10c09-12c4872fa-bb74-444e-96d6-12ba4dddf56a-19eeb9f6d-a656-4177-992c-f89dd89fe5f6-1c2131491-6815-4839-8ae8-8b272a198cb7-1524237316002020-08-19T14:41:24Z2020-08-19T14:41:24Z2017-06-02Mechanical 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.application/pdfhttps://doi.org/10.1172/jci.insight.86507ISSN: 2379-3708https://repository.urosario.edu.co/handle/10336/27224engAmerican Society for Clinical InvestigationNo. 11Art.e86507 JCI InsightVol. 2JCI Insight, ISSN 2379-3708, Vol.2, No.11 (June, 2017); 15 pp., Art.e86507https://insight.jci.org/articles/view/86507/pdfhttp://jci.me/86507-pdfAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf2JCI Insightinstname:Universidad del Rosarioreponame:Repositorio Institucional EdocURUse of ZincTreatment of lung conditionsLessons from mechanical lung ventilationZinc deficiency primes the lung for ventilator-induced injuryLa deficiencia de zinc prepara al pulmón para las lesiones inducidas por el ventiladorarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Boudreault, FrancisPinilla-Vera,MiguelEnglert, Joshua A.Kho,Alvin T.Isabelle, ColleenArciniegas, Antonio J.Barragan-Bradford, DianaQuintana, CarolinaGuan, JiazhenMoo Choi, KyoungRegistry, MICUSholl, LynetteHurwitz, ShelleyTschumperlin, Daniel J.Baron, Rebecca M.Amador Muñoz, Diana PatriciaORIGINAL86507-1-20170602070656-covered-253bed37ca4c1ab43d105aefdf7b5536.pdfapplication/pdf1347943https://repository.urosario.edu.co/bitstreams/b392c053-c6b4-4f0c-b799-bea25571350a/downloade2a271312ed6e296edf3edc28dd7517dMD51TEXT86507-1-20170602070656-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf.txt86507-1-20170602070656-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf.txtExtracted texttext/plain63301https://repository.urosario.edu.co/bitstreams/32b75bad-0b0b-460c-9fba-336e682903fa/download128e73cd283fcabbc28d3e842c12d443MD52THUMBNAIL86507-1-20170602070656-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf.jpg86507-1-20170602070656-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf.jpgGenerated Thumbnailimage/jpeg4835https://repository.urosario.edu.co/bitstreams/67c4cdf1-073f-4b42-851a-0a576a1eb264/downloadce1794ad2c32f855d6215f9d4d11ca90MD5310336/27224oai:repository.urosario.edu.co:10336/272242021-06-03 00:50:08.261https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |