Molecular signatures of trauma-hemorrhagic shock-induced lung injury: hemorrhage- and injury-associated genes.
The etiology of trauma-hemorrhagic shock (T/HS)-induced acute lung injury has been difficult to elucidate because of, at least in part, the inability of in vivo studies to separate the noninjurious pulmonary effects of trauma-hemorrhage from the tissue-injurious ones. To circumvent this in vivo limitation, we used a model of T/HS in which T/HS lung injury was abrogated by dividing the mesenteric lymph duct. In this way, it was possible to separate the pulmonary injurious response from the noninjurious systemic response to T/HS by comparing the pulmonary molecular responses of rats subjected to T/HS, which did and did not develop lung injury, with those of nonshocked rats. Using high-density oligonucleotide arrays and treatment group comparisons of whole lung tissue collected at 3 h after the end of the shock or sham-shock period, 139 of 8,799 assessed genes were identified by significant analysis of microarrays. Hemorrhage without the secondary effects of lung injury modulated the expression of 21 genes such as interleukin 1beta, metallothionein-2, and myeloctomatosis oncogene (c-myc). In response to injury, 42 genes were identified to be differentially expressed. Upregulated genes included the L1 retroposon and guanine deaminase, whereas downregulated genes included catalase and superoxide dismutase 1. Real-time polymerase chain reaction confirmed the differential expression for selected genes. PathwayAssist analysis identified interleukin 1beta as a central regulator of two subpathways of stress response-related genes (c-myc and superoxide dismutase 1/catalase) as well as several unrelated genes such as lipoprotein lipase. Our model system provided a unique opportunity to distinguish the molecular changes associated with T/HS-induced acute lung injury from the systemic molecular response to T/HS.
Feinman
Rena
R
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA. feinmarr@umdnj.edu
Deitch
Edwin A
EA
Aris
Virginie
V
Chu
Hung B
HB
Abungu
Billy
B
Caputo
Francis J
FJ
Galante
Anthony
A
Xu
DaZhong
D
Lu
Qi
Q
Colorado
Iriana
I
Streck
Deanna
D
Dermody
James
J
Soteropoulos
Patricia
P
D000818:Animals; D020869:Gene Expression Profiling; D008026:Ligation; D008168:Lung / Q000378:metabolism*; D042601:Lymphatic Vessels; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology