Role of c-kit receptor tyrosine kinase-mediated signal transduction in proliferation of bile epithelial cells in young rats after ligation of bile duct: a study using Ws/Ws c-kit mutant rats.
OBJECTIVE
Recently, it has been shown that the c-kit receptor tyrosine kinase (KIT) is expressed 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 rats, whose KIT kinase activity was severely impaired, could proliferate in response to bile stasis after BDL.


RESULTS
When 2-week-old control normal (+/+) and Ws/Ws mutant rats underwent BDL, only a few BEC were found in the portal field of livers of Ws/Ws rats, whereas many BEC 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 in +/+ 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.


CONCLUSIONS
The mechanism whereby BEC proliferate in response to bile stasis after BDL may be different between 2- and 6-week-old rats, and KIT mediated-signal transduction plays a crucial role in the proliferation of immature BEC in young rats.
Satake
Makoto
M
Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Shimano
Koichi
K
Yamamoto
Takashi
T
Okaya
Atsuhito
A
Iwasaki
Teruo
T
Kakihana
Michiko
M
Fujimoto
Jiro
J
Terada
Nobuyuki
N
Tsujimura
Tohru
T
D000367:Age Factors; D000818:Animals; D001652:Bile Ducts / Q000166:cytology*; D002455:Cell Division / Q000502:physiology; D002779:Cholestasis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D015398:Signal Transduction / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit