Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray.
OBJECTIVE
The liver has the capacity to regenerate after partial hepatectomy. In order to clarify the mechanism of liver regeneration, we observed the initial stage, especially the mechanism of gene expression during progress from G0 to S phase (0-24 h), and attempted to identify new genes controlling progress to the S phase.


METHODS
We applied large-scale gene expression analysis with complementary DNA microarrays in mouse hepatectomy models to clarify the mechanism of liver regeneration after partial hepatectomy.


RESULTS
As a result, 23 new immediate-early gene candidates such as interleukin-1 receptor associated kinase-1 and karyopherin alpha-1, which are involved in transportation within the nucleus, were discovered. Candidates for new genes concerned with the progress to the S phase were discovered: inhibitor of DNA binding 2 (ID2) and inhibitor of DNA binding 3 (ID3), both new liver regeneration factors that promoted progress to the S phase, and GADD45 gamma (growth arrest and DNA-damage-inducible protein) as a factor inhibiting that process.


CONCLUSIONS
The above results not only suggest the importance of NFkappaB in the initial stage of liver regeneration but also points to the orderly maintenance of the proliferation of the cells in liver regeneration.
Togo
Shinji
S
Department of Surgery II, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. togo@med.yokohama-cu.ac.jp
Makino
Hirochika
H
Kobayashi
Takatoshi
T
Morita
Tomoyuki
T
Shimizu
Tetsuya
T
Kubota
Toru
T
Ichikawa
Yasushi
Y
Ishikawa
Takashi
T
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Shimada
Hiroshi
H
D000818:Animals; D015870:Gene Expression; D020869:Gene Expression Profiling; D017781:Genes, Immediate-Early; D006498:Hepatectomy / Q000379:methods; D066298:In Vitro Techniques; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation