TY - JOUR
T1 - Gene expression profiling of target genes in ventilator-induced lung injury
AU - Dolinay, Tamás
AU - Kaminski, Naftali
AU - Felgendreher, Martina
AU - Kim, Hong P.
AU - Reynolds, Paul
AU - Watkins, Simon C.
AU - Karp, Dörte
AU - Uhlig, Stefan
AU - Choi, Augustine M.K.
PY - 2006/6/16
Y1 - 2006/6/16
N2 - In the lungs, high-pressure mechanical ventilation induces an inflammatory response similar to that observed in acute respiratory distress syndrome. To further characterize these responses and to compare them with classical inflammatory pathways, we performed gene expression profiling analysis of 20,000 mouse genes in isolated blood-free (to exclude genes from sequestered leukocytes) perfused mouse lungs exposed to low-pressure ventilation (10 cmH2O), high-pressure ventilation (25 cmH2O, overventilation), and LPS treatment. A large number of inflammatory and apoptotic genes were increased by both overventilation and LPS. However, certain growth factor-related genes, as well as genes related to development, cellular communication, and the cytoskeleton, were only regulated by overventilation. We validated and confirmed increased mRNA expression pattern of five genes (amphiregulin, gravin, Nur77, Cyr61, interleukin-11) by real-time PCR; furthermore, we confirmed increased protein expression of amphiregulin by immunohistochemistry and immunoblotting assays. These genes represent novel candidate genes in ventilator-induced lung injury.
AB - In the lungs, high-pressure mechanical ventilation induces an inflammatory response similar to that observed in acute respiratory distress syndrome. To further characterize these responses and to compare them with classical inflammatory pathways, we performed gene expression profiling analysis of 20,000 mouse genes in isolated blood-free (to exclude genes from sequestered leukocytes) perfused mouse lungs exposed to low-pressure ventilation (10 cmH2O), high-pressure ventilation (25 cmH2O, overventilation), and LPS treatment. A large number of inflammatory and apoptotic genes were increased by both overventilation and LPS. However, certain growth factor-related genes, as well as genes related to development, cellular communication, and the cytoskeleton, were only regulated by overventilation. We validated and confirmed increased mRNA expression pattern of five genes (amphiregulin, gravin, Nur77, Cyr61, interleukin-11) by real-time PCR; furthermore, we confirmed increased protein expression of amphiregulin by immunohistochemistry and immunoblotting assays. These genes represent novel candidate genes in ventilator-induced lung injury.
KW - Acute respiratory distress syndrome
KW - Gene expression analysis
KW - Overventilation
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U2 - 10.1152/physiolgenomics.00110.2005
DO - 10.1152/physiolgenomics.00110.2005
M3 - Article
C2 - 16569776
AN - SCOPUS:33745660525
VL - 26
SP - 68
EP - 75
JO - Physiological Genomics
JF - Physiological Genomics
SN - 1094-8341
IS - 1
ER -