Apoptosis is involved in the homeostatic control of organs. The aim of this study was to define the in vivo role of apoptosis-related proteins including the Fas system and Bcl-2 in liver regeneration following a partial hepatectomy (PH). We used 70% hepatectomized rats which were serially sacrificed from 12 h to 28 days. The expressions of Fas, Fas ligand, and Bcl-2 were examined by semiquantitative RT-PCR and immunohistochemistry. Liver regeneration, as examined by PCNA staining, peaked from 24 h to day 3, and declined from day 5. On the other hand, hepatocyte apoptosis, as examined by TUNEL staining, was seldom observed until 24 h, but increased from 1 week after PH. In the RT-PCR study, Fas showed an early decline by 24 h, followed by a later peak from days 3 to 5, and then a constant expression thereafter. Meanwhile, the Fas ligand was also low until day 3, but showed a remarkable increase from days 5 to 7, followed by a gradual decrease. On the other hand, Bcl-2 showed an early peak until 24 h, followed by a decline from day 5. In an immunohistochemical study, the time courses of these protein expressions were almost synchronous with their mRNAs in the RT-PCR study. We thus conclude that the coordinated interplay between these apoptosis-related proteins and hepatocyte apoptosis suggests the possible involvement of these proteins in the course of liver regeneration.

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