Contributions of hepatocytes and bile ductular cells in ductular reactions and remodeling of the biliary system after chronic liver injury.
著者
永濱, 康晴
(Nagahama, Yasuharu)
Sone, Masayuki
Xi, Chen
岡田, 陽子
(Okada, Yoko)
山本, 雅大
(Yamamoto, Masahiro)
Bing, Xin
Matsuo, Yasuhiro
Komatsu, Mikiko
Suzuki, Akira
Enomoto, Katsuhiko
西川, 祐司
(Nishikawa, Yuji)
上位タイトル
The American Journal of Pathology
Vol.184,
No.11
(2014.
11)
,p.3001-
3012
識別番号
ISSN
0002-9440
DOI
10.1016/j.ajpath.2014.07.005
その他
PMID:25193593
抄録
Mature hepatocytes are suggested to possess a capacity for bile ductular transdifferentiation, but whether and how hepatocytes contribute to ductular reaction in chronic liver diseases has not been elucidated. We examined whether mouse hepatocytes can transdifferentiate into bile ductular cells in vitro, using a three-dimensional collagen gel culture method, and in vivo, using a liver repopulation model in which β-galactosidase-positive hepatocytes from Alb-Cre × ROSA26R mice were transplanted into the liver of wild-type mice. We further examined the relative contribution of intrinsic hepatocytes in ductular reaction in a hepatocyte lineage-tracing model using Mx1-Cre × ROSA26R mice treated with polyinosinic-polycytidylic acid. Within collagen gels, hepatocytes exhibited branching morphogenesis associated with the emergence of bile duct-like phenotype. In the liver repopulation model, many β-galactosidase-positive, hepatocyte-derived bile ductular structures were identified; these markedly increased after liver injury. In Mx1-Cre × ROSA26R mice, relatively minor but significant contributions of hepatocyte-derived bile ductules were observed in both periportal and centrilobular ductular reaction. As the centrilobular ductular reaction progressed, the portal ducts or ductules migrated toward the injured area and joined with hepatocyte-derived ductules, leaving the portal tract without biliary structures. We conclude that hepatocytes and bile ducts or ductules are important sources of ductular reaction and that the intrahepatic biliary system undergoes remarkable remodeling in response to chronic liver injury.
