Novel transcript profiling of diffuse alveolar damage induced by hyperoxia exposure in mice: normalization by glyceraldehyde 3-phosphate dehydrogenase.
Under mechanical ventilation with high-inspired oxygen concentration, diffuse alveolar damage was found to take place in some patients. To clarify the molecular pathophysiology of this condition, we investigated the time course of gene expression changes induced by hyperoxia exposure in mouse lung using real-time quantitative polymerase chain reaction (qPCR). Our results normalized by glyceraldehyde 3-phosphate dehydrogenase showed that mRNA levels of cysteine rich protein 61 (CYR61) and connective tissue growth factor (CTGF) were significantly upregulated, while those of surfactant-associated protein C (SFTPC), cytochrome P450, 2F2 (CYP2F2), Claudin 1, (CLDN1), membrane-associated zonula occludens protein-1 (ZO-1), lysozyme (LYZS), and P lysozyme structural (LZP-S) were significantly downregulated. Increasing level of mRNAs, each encoding CYR61 and CTGF, suggests a serious risk of fibrosing alveolitis. Decrease in levels of mRNAs for SFTPC, CYP2F2, CLDN1, ZO-1, LYZS, and LZP-S suggests alveolar dysfunction and disruption of the immune system. Moreover, we confirmed apoptotic conditions, such as significant upregulations of mRNA levels in Myc and Galectin-3. Hyperoxic condition probably yielded reactive oxygen species (ROS), which resulted in a malignant cycle of ROS production by Myc overexpression.
Shimada
Ichiroh
I
Department of Forensic Medicine, Faculty of Medical Sciences, University of Fukui, 23-3, Matsuokashimoaizuki, eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan. ichi@u-fukui.ac.jp
Matsui
Kazuhiro
K
Brinkmann
Bernd
B
Hohoff
Carsten
C
Hiraga
Koichi
K
Tabuchi
Yoshiaki
Y
Takasaki
Ichiro
I
Kato
Ichiro
I
Kawaguchi
Hiroshi
H
Takasawa
Kumi
K
Iida
Reiko
R
Takizawa
Hisao
H
Matsuki
Takasumi
T
D000818:Animals; D062445:Claudin-1; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018496:Hyperoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein
D062445:Claudin-1; C568113:Cldn1 protein, mouse; D055515:Cysteine-Rich Protein 61; D037502:Galectin 3; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C489428:Myc protein, mouse; D010455:Peptides; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; C489680:Sftpc protein, mouse; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D055513:Connective Tissue Growth Factor; D003577:Cytochrome P-450 Enzyme System; C055686:glyceraldehyde 3-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D009113:Muramidase