Background: Activating transcription factor-4 (ATF4)-also termed CREB2, C/ATF, and TAXREB67-is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting.
Oval cells that develop in the rat 2-acetylaminofluorene/ partial hepatectomy (AAF/PH) model express the c-kit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF). We investigated the role of the SCF/KIT system in the development of oval cells using Ws/Ws rats, whose c-kit kinase activity was severely impaired owing to a small deletion in the kinase domain. On days 7, 9, and 13 after PH in the AAF/PH model, the development Mature hepatocytes proliferate after partial hepatectomy (PH), resulting in regeneration of the liver. In contrast, if PH is performed under conditions in which the replication of mature hepatocytes is impaired, oval cells that are assumed to develop from hepatic stem cells located in the canal of Hering (biliary ductule) proliferate instead of mature hepatocytes and infiltrate into the surrounding parenchyma.
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