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ATF3 is activated in ventilator induced lung injury
Author(s) -
Dos Santos Claudia,
Akram Ali,
Masoom Hussain,
Han Bing,
Haitsma Jack J.,
Peng Claudia,
Shan Yuexin,
Zhang Haibo,
Liu Mingyao,
Hai Tsonwin,
Slutsky Arthur S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.612.14
Subject(s) - atf3 , western blot , in vivo , microarray analysis techniques , microarray , microbiology and biotechnology , biology , chemistry , gene expression , gene , promoter , biochemistry , genetics
Mechanical ventilation (MV) has been shown to cause ventilator‐induced lung injury (VILI). We wanted to identify novel molecular targets involved in reducing the harmful effects of MV (VILI). Methods To identify potential novel genes and proteins involved in VILI we i) performed microarray analysis on previously published VILI animal model data, ii) exposed human bronchial epithelial cells (Beas‐2b) in vitro to mechanical cyclic stretch (30 cycles/min for 4 hours), iii) performed western blot analysis on these stretched and non‐stretched cells, and iv) validated the regulation of the newly discovered gene(s) in vivo using wild type (WT) and ATF3 (Activator transcription factor 3) knock‐out mice (ATF3 KO). These two groups of mice were exposed to either injurious or non‐injurious ventilation strategies in combination with LPS or saline. Results ATF3 was identified by microarray analysis as one of the main genes involved in VILI. The presence of this factor was validated in vitro in the mechanically cyclic‐stretched Beas‐2b cells. Western blot assays confirmed expression of ATF3 in the stretched cells and their absence in the static cells. We further confirmed the regulation of ATF3 using WT and ATF3 KO mice in a model of VILI in vivo . ATF3 KO mice exposed to LPS in combination with injurious MV had more inflammation than WT mice of similar treatment or mice treated with saline. Conclusion Expression of ATF3 is stretch dependent and this gene seems to confer protection in combination with MV. Specific targeting of this factor in clinical settings could reduce VILI in patients receiving MV.