Gene Expression During Liver Regeneration After Partial Hepatectomy in Mice Lacking Type 1 Tumor Necrosis Factor Receptor

• Published in: The Journal of surgical research 2009-04, Vol.152 (2), p.178-188
• Main Authors: Shimizu, Tetsuya, M.D, Togo, Shinji, M.D., Ph.D, Kumamoto, Takahumi, M.D, Makino, Hirochika, M.D., Ph.D, Morita, Tomoyuki, M.D., Ph.D, Tanaka, Kuniya, M.D., Ph.D, Kubota, Toru, M.D., Ph.D, Ichikawa, Yasushi, M.D., Ph.D, Nagasima, Youji, M.D., Ph.D, Okazaki, Yasushi, M.D., Ph.D, Hayashizaki, Yoshihide, M.D., Ph.D, Shimada, Hiroshi, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Alkaline Phosphatase - blood; Animals; Biological and medical sciences; cDNA microarray; Cell Cycle - genetics; DNA, Complementary - genetics; Gene Expression Regulation; General aspects; Hepatectomy - methods; Hepatectomy - mortality; Immunohistochemistry; Interleukin-6 - blood; Ki-67 Antigen - analysis; Liver - cytology; Liver - immunology; liver regeneration; Liver Regeneration - genetics; Liver Regeneration - physiology; Liver, biliary tract, pancreas, portal circulation, spleen; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; partial hepatectomy; Receptors, Tumor Necrosis Factor, Type I - deficiency; RNA - genetics; RNA - isolation & purification; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Survival Rate; TNFR-1 knockout mouse
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2007.12.785

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