title: Nucleostemin in injury-induced liver regeneration.
abstract: The high regenerative capacity of liver contributes to the maintenance of its size and function when injury occurs. Partial hepatectomy induces division of mature hepatocytes to maintain liver function, whereas severe injury stimulates expansion of undifferentiated hepatic precursor cells, which supply mature cells. Although several factors reportedly function in liver regeneration, the precise mechanisms underlying regeneration remain unclear. In this study, we analyzed expression of nucleostemin (NS) during development and in injured liver by using transgenic green fluorescent protein reporter (NS-GFP Tg) mice. In neonatal liver, the hepatic precursor cells that give rise to mature hepatocytes were enriched in a cell population expressing high levels of NS. In adult liver, NS was abundantly expressed in mature hepatocytes and rapidly upregulated by partial hepatectomy. Severe liver injury promoted by a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine induced the emergence of NS-expressing ductal epithelial cells as hepatic precursor cells. NS knockdown inhibited both hepatic colony formation in vitro and proliferation of hepatocytes in vivo. These data strongly suggest that NS plays a critical role in regeneration of both hepatic precursor cells and hepatocytes in response to liver injury.
authors: Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors: Haruhiko
authors: H
authors: Shugo
authors: Takako
authors: T
authors: Ooshio
authors: Masako
authors: M
authors: Naito
authors: Kazuhito
authors: K
authors: Naka
authors: Takayuki
authors: T
authors: Hoshii
authors: Yuko
authors: Y
authors: Tadokoro
authors: Teruyuki
authors: T
authors: Muraguchi
authors: Akira
authors: A
authors: Tamase
authors: Noriyuki
authors: N
authors: Uema
authors: Taro
authors: T
authors: Yamashita
authors: Yasunari
authors: Y
authors: Nakamoto
authors: Toshio
authors: T
authors: Suda
authors: Shuichi
authors: S
authors: Kaneko
authors: Atsushi
authors: A
authors: Hirao
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D004032:Diet; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D019204:GTP-Binding Proteins; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006498:Hepatectomy; D006500:Hepatic Duct, Common / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000293:injuries* / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity; D016601:RNA-Binding Proteins; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; D002352:Carrier Proteins; D009687:Nuclear Proteins; D011725:Pyridines; D016601:RNA-Binding Proteins; C470311:nucleostemin protein, mouse; D049452:Green Fluorescent Proteins; D019204:GTP-Binding Proteins