title: Immunohistochemical analyses of cell cycle progression and gene expression of biliary epithelial cells during liver regeneration after partial hepatectomy of the mouse.
abstract: The liver has a remarkable regeneration capacity, and, after surgical removal of its mass, the remaining tissue undergoes rapid regeneration through compensatory growth of its constituent cells. Although hepatocytes synchronously proliferate under the control of various signaling molecules from neighboring cells, there have been few detailed analyses on how biliary cells regenerate for their cell population after liver resection. The present study was undertaken to clarify how biliary cells regenerate after partial hepatectomy of mice through extensive analyses of their cell cycle progression and gene expression using immunohistochemical and RT-PCR techniques. When expression of PCNA, Ki67 antigen, topoisomerase IIα and phosphorylated histone H3, which are cell cycle markers, was immunohistochemically examined during liver regeneration, hepatocytes had a peak of the S phase and M phase at 48-72 h after resection. By contrast, biliary epithelial cells had much lower proliferative activity than that of hepatocytes, and their peak of the S phase was delayed. Mitotic figures were rarely detectable in biliary cells. RT-PCR analyses of gene expression of biliary markers such as Spp1 (osteopontin), Epcam and Hnf1b demonstrated that they were upregulated during liver regeneration. Periportal hepatocytes expressed some of biliary markers, including Spp1 mRNA and protein. Some periportal hepatocytes had downregulated expression of HNF4α and HNF1α. Gene expression of Notch signaling molecules responsible for cell fate decision of hepatoblasts to biliary cells during development was upregulated during liver regeneration. Notch signaling may be involved in biliary regeneration.
authors.affiliation: Department of Biology, Faculty of Science, Shizuoka University, Oya 836, Suruga-ku, Shizuoka city, Shizuoka 422-8529, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuda
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuchi
authors.forename: Shinomi
authors.initials: S
authors.lastname: Yagi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shiojiri
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001652:Bile Ducts / Q000166:cytology*; D002453:Cell Cycle; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D004250:DNA Topoisomerases, Type II