Gene expression during liver regeneration after partial hepatectomy in mice lacking type 1 tumor necrosis factor receptor.
BACKGROUND
To investigate the function of tumor necrosis factor-alpha (TNF-alpha) during hepatocyte proliferation, we studied liver regeneration following partial hepatectomy in mice lacking type 1 TNF receptor (TNFR-1).


METHODS
TNFR-1 knockout (KO) and wild-type mice were subjected to partial (two-thirds) hepatectomy. Liver regeneration was evaluated by assessing liver weights and Ki67 immunohistochemistry. Riken complementary DNA microarray analysis was performed for liver samples from mice undergoing partial hepatectomy to better compare different mouse partial hepatectomy models (TNFR-1 KO mice, KO group; and wild-type mice, W group).


RESULTS
Liver weight was regained after 14 days in the KO group, and after 7 days in the W group. Genes including lipopolysaccharide, toll-like receptor 4 precursor, mitogen-activated protein kinase kinase kinase 4, mitogen-activated protein kinase kinase kinase kinase 4, and mitogen-activated protein kinase 8-interacting protein were up-regulated in the KO group. As for the cell-cycle-regulated genes, the levels of cyclin D1, nuclear factor-kappa B light chain, and TNF receptor super family membrane 1a were down-regulated in the KO group. Microarray analysis showed decreased activities of the hexokinase- and phospho-fructokinase-related glycolytic pathways in the KO group.


CONCLUSIONS
These results contribute to the better understanding of the mechanisms of liver regeneration after partial hepatectomy in TNFR-1 KO mice.
Shimizu
Tetsuya
T
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Togo
Shinji
S
Kumamoto
Takahumi
T
Makino
Hirochika
H
Morita
Tomoyuki
T
Tanaka
Kuniya
K
Kubota
Toru
T
Ichikawa
Yasushi
Y
Nagasima
Youji
Y
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Shimada
Hiroshi
H
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006498:Hepatectomy / Q000379:methods* / Q000401:mortality; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000276:immunology; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency*; D015996:Survival Rate
D018076:DNA, Complementary; D015850:Interleukin-6; D019394:Ki-67 Antigen; D047888:Receptors, Tumor Necrosis Factor, Type I; D012313:RNA; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase