Co-Investigator(Kenkyū-buntansha) |
MAKINO Ichiro Miyazaki Medical College, Surgery 1, Assistant Professor, 医学部, 助手 (30347059)
KAI Masahiro Miyazaki Medical College, Surgery 1, Assistant Professor, 医学部, 助手 (40264379)
KONDO Kazuhiro Miyazaki Medical College, Surgery 1, Assistant Professor, 医学部, 助手 (10244196)
UEDA Junji Miyazaki Medical College, Surgery 1, Medical Staff, 医学部, 医員
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Research Abstract |
1) We investigated the differences in the transcription factors and cell cycle regulators between obstructive jaundiced and control rats before and after hepatectomy. The expressions and activities of C/EBP-α and ?β were significantly decreased associated with the significantly lower cyclin E expression after hepatectomy in the jaundiced group than in the controls. The activities of AP-1, cyclin D1, and p21 were not significantly different between the two groups. These results suggest that obstructive jaundice inhibits hepatic expression and activities of C/EBP, resulting in the impaired cyclin E expression that is partly responsible for the cell cycle dysfunction after hepatectomy. (Reference 1) 2) Regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-third hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The activities of C/EBP and AP- 1 were significantly inhibited in the cirrhotic gr
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oup compared with those in the control group, but not those of NF-kB and STAT 3. The expression of cyclin D1, E, and A was significantly decreased in the cirrhotic group compared with the control group. These results suggest that downregulation of cyclin D1, E, and A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy. (Reference 2) 3) The importance of bile in liver regeneration after hepatectomy is known. Bile was drained externally (ED group) or into the duodenum (ID group) for 7 days before 70% hepatectomy, and liver regeneration was assessed by the relative liver weight, DNA synthesis rate, and PCNA labeling index. Posthepatectomy expressions of cyclin D1 and E, and cyclin D1- and E-associated kinase activity were also analyzed. Liver regeneration in the ED group was delayed than that in the ID group. Cyclin D1 and E expression and cyclin D1-associated kinase activity were not different between the two groups. Cyclin E-associated kinase activity was lower in the ID group than the ED group at 18 hr after hepatectomy. These results suggest the absence of intestinal bile delays liver regeneration associated with cyclin E-associated kinase inactivation after hepatectomy. (Reference 3) Less
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