Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study.
Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4099342?pdf=render |
| _version_ | 1819017383588659200 |
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| author | Sashko Spassov Dietmar Pfeifer Karl Strosing Stefan Ryter Matthias Hummel Simone Faller Alexander Hoetzel |
| author_facet | Sashko Spassov Dietmar Pfeifer Karl Strosing Stefan Ryter Matthias Hummel Simone Faller Alexander Hoetzel |
| author_sort | Sashko Spassov |
| collection | DOAJ |
| description | Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million). Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection. |
| first_indexed | 2024-12-21T03:02:39Z |
| format | Article |
| id | doaj.art-6b95fbae333a40ed9977d2847b43c9ba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T03:02:39Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6b95fbae333a40ed9977d2847b43c9ba2022-12-21T19:18:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10240110.1371/journal.pone.0102401Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study.Sashko SpassovDietmar PfeiferKarl StrosingStefan RyterMatthias HummelSimone FallerAlexander HoetzelRecently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million). Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection.http://europepmc.org/articles/PMC4099342?pdf=render |
| spellingShingle | Sashko Spassov Dietmar Pfeifer Karl Strosing Stefan Ryter Matthias Hummel Simone Faller Alexander Hoetzel Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. PLoS ONE |
| title | Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. |
| title_full | Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. |
| title_fullStr | Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. |
| title_full_unstemmed | Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. |
| title_short | Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study. |
| title_sort | genetic targets of hydrogen sulfide in ventilator induced lung injury a microarray study |
| url | http://europepmc.org/articles/PMC4099342?pdf=render |
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