Comprehensive analysis of differential gene expression profiles on D-galactosamine-induced acute mouse liver injury and regeneration.
Microarray analysis of RNA from d-galactosamine (GalN)-administered mouse livers was performed to establish a global gene expression profile during injury and regeneration stages at two different doses. A single dose of GalN at 266 or 26.6 mg/kg body weight was given intraperitoneally, and the liver samples were obtained after 6, 24, and 72 h. Histopathologic studies enabled the classification of the D-galactosamine effect into injury (6, 24 h) and regeneration (72 h) stages. By using the Applied Biosystems mouse genome survey microarray, a total of 7267 out of 33,315 (21.8%) genes were found to be statistically reliable at p<0.05 by two-way ANOVA, and 1469 (4.4%) probes at false discovery rate <5% by significance analysis of microarray. Among the statistically reliable clones by both analytical methods, 389 genes were differentially expressed when compared with non-treated control, with more than a 1.625-fold difference (which equals 0.7 in log(2) scale) at one or more GalN treatment conditions and with less than 1.625-fold difference at all three vehicle-treated conditions. Three hundred thirty six genes and 13 genes were identified as injury- and regeneration-specific genes, respectively, showing that most of the transcriptomic changes were seen during the injury stage. Furthermore, multiple genes involved in protein synthesis and degradation, mRNA processing and binding, and cell cycle regulation showed variable transcript levels upon acute GalN administration.
Chung
Heekyoung
H
Department of Pathology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Kim
Hyun-Jun
HJ
Jang
Ki-Seok
KS
Kim
Mingoo
M
Yang
Jungeun
J
Kang
Kyung-Sun
KS
Kim
Hyung-Lae
HL
Yoon
Byung-Il
BI
Lee
Mi-Ock
MO
Lee
Byung-Hoon
BH
Kim
Ju Han
JH
Lee
Yong-Sung
YS
Kong
Gu
G
D000208:Acute Disease; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005688:Galactosamine / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D005688:Galactosamine