Impaired Hepatocyte DNA Synthetic Response Posthepatectomy in Insulin-Like Growth Factor Binding Protein 1-Deficient Mice with Defects in C/EBPβ and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Regulation

• DOI: 10.1128/mcb.23.4.1251-1259.2003
• Publication Date: 2003-01-29T22:44:28Z
• Authors: Julia I. Leu; Mary Ann S. Crissey; Linden E. Craig; Rebecca Taub
• Keywords: Liver Regeneration

After a two-thirds hepatectomy, normally quiescent liver cells are stimulated to reenter the cell cycle and proliferate restore original mass. One of most rapidly highly induced genes proteins in regenerating is insulin-like growth factor binding protein 1 (IGFBP-1), secreted that may modulate activities factors (IGFs) or signal via IGF-independent mechanisms. To assess functional role IGFBP-1 regeneration, mice with targeted disruption gene were generated. Although IGFBP-1(-/-) demonstrated normal development, they had abnormal regeneration after partial characterized by necrosis reduced delayed hepatocyte DNA synthesis. The regenerative response was associated blunted activation mitogen-activated kinase/extracellular signal-regulated kinase (MAPK/ERK) induction C/EBP beta expression posthepatectomy. Like abnormalities observed hepatectomized beta(-/-) mice, cyclin A B1 livers, whereas D1 normal. Treatment preoperative dose MAPK/ERK expression, suggesting support at least part its effect on activities. These findings first demonstration involvement regulation vivo mitogenic signaling pathways.