Analysis of liver regeneration : A study using c-kit mutants

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We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration. BM cells of green fluorescent protein (GFP) transgenic mice were transplanted into W/W^v c-kit mutant mice after whole-body irradiation. In the resulting W/W^v (BMT-W/W^v) mice, GFP positive cells were observed at the periportal region. When CCl_4 or anti-Fas antibody was administered to BMT-W/W^v mice, GFP positive cells developed along liver sinusoid. These results suggest that BM cells differentiate to sinusoid endothelial cells during liver regeneration.Recently, it has been shown that the expression of c-kit receptor tyrosine kinase (KIT) is seen in the liver of young rats, and its expression is up-regulated in bile epithelial cells (BEC) after ligation of the common bile duct (BDL). To clarify a role of KIT in BEC, we examined whether BEC of Ws/Ws c-kit mutant rats could proliferate in response to bile stasis after BDL. When 2-week-old normal (+/+) and Ws/Ws rats underwent BDL, only a few BEC were found in the portal field of livers of Ws/Ws rats, whereas many BBC were found in that of +/+ rats. Furthermore, Ki-67 immunostaining showed that the proliferative activity of BEC in 2-week-old Ws/Ws rats was much lower than that of +/+ rats of the same age. In contrast, when 6-week-old +/+ and Ws/Ws rats underwent BDL, BEC similarly proliferated in the livers of +/+ and Ws/Ws rats, and the proliferative activity of BEC was comparable. It is likely that the mechanism whereby BEC proliferate in response to bile stasis after BDL is different between 2-week-old and 6-week-old rats, and KIT mediated-signal transduction plays a crucial role in the proliferation of immature BEC in young rats.