Contributions of hepatocytes and bile ductular cells in ductular reactions and remodeling of the biliary system after chronic liver injury
| Autor: | Yoko Okada, Masahiro Yamamoto, Masayuki Sone, Bing Xin, Xi Chen, Akira Suzuki, Katsuhiko Enomoto, Yuji Nishikawa, Yasuharu Nagahama, Mikiko Komatsu, Yasuhiro Matsuo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Cell lineage digestive system Pathology and Forensic Medicine Mice Branching morphogenesis medicine Animals Cell Lineage Biliary Tract Liver injury Chemistry Liver Diseases Transdifferentiation 学位授与年月日：平成26年12月25日 medicine.disease Liver repopulation digestive system diseases Collagen gel 旭川医科大学：博士（医学）（乙第454号） medicine.anatomical_structure Hepatocyte Cell Transdifferentiation Hepatocytes Bile Ducts Chronic liver injury |
| Zdroj: | The American Journal of Pathology. 184(11):3001-3012 |
| ISSN: | 0002-9440 |
| Popis: | 著者最終原稿 CC-BY-NC-ND 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|