Analysis of gene expression profiles in fatal hepatic failure after hepatectomy in mice.
BACKGROUND
We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy.


METHODS
Ribonucleic acid (RNA)s from the remnant hepatic tissue of 70%- and 90%-hepatectomized mice were labeled with fluorescent dyes, and hybridized to the Riken set of 39,168 full-length enriched mouse cDNA arrays. The gene expression profiles in 90%- and 70%-hepatectomized mice were analyzed by scanning date for fluorescent dye signals.


RESULTS
The down-regulated genes in 90%-hepatectomized mice were genes activating extracellular matrix (ECM) remodeling (matrix metalloproteinases, laminins, and integrins), genes related to cytokines (tumor necrosis factor α converting enzyme, and Janus kinase 3) that were related to the priming, genes related to growth factor (heparin-binding epidermal growth factor-like growth factor and others), and genes promoting cell cycle progression (cyclin D1, D2, and E2) that were related to the progression of hepatocytes. The up-regulated genes were genes inhibiting ECM remodeling [plasminogen activator inhibitors (PAIs)].


CONCLUSIONS
Hepatic failure after hepatectomy was characterized by the inhibition of hepatic cell cycle priming and progression both induced by ECM remodeling in liver regeneration. Particularly, the overexpression of PAIs was thought to play the major role in the first step of inhibition of ECM remodeling.
Makino
Hirochika
H
Department of Gastroenterological Surgery, Yokohama City University School Graduate of Medicine, Yokohama, Japan. hirochik@urahp.yokohama-cu.ac.jp
Shimada
Hiroshi
H
Morioka
Daisuke
D
Kunisaki
Chikara
C
Morita
Tomoyuki
T
Matsuyama
Ryusei
R
Kubota
Toru
T
Shimizu
Daisuke
D
Ichikawa
Yasushi
Y
Tanaka
Kuniya
K
Matsuo
Kenichi
K
Togo
Shinji
S
Endo
Itaru
I
Nagashima
Youji
Y
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D020869:Gene Expression Profiling; D006498:Hepatectomy; D022781:Hepatocytes / Q000473:pathology; D017093:Liver Failure / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D015849:Plasminogen Inactivators / Q000502:physiology
D015849:Plasminogen Inactivators