title: Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study.
abstract: 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.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Sashko
authors.initials: S
authors.lastname: Spassov
authors.affiliation: Genomics Core Lab, Dept. Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Strosing
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ryter
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Faller
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoetzel
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D055370:Lung Injury / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
chemical_list: D006862:Hydrogen Sulfide