title: HSCs play a distinct role in different phases of oval cell-mediated liver regeneration.
abstract: Hepatic stem cell niche plays an important role in hepatic oval cell-mediated liver regeneration. As a component of hepatic stem cell niche, the role of hepatic stellate cells (HSCs) in oval cell proliferation needs further studies. In the present study, we isolated HSCs from rats at indicated time point after partial hepatectomy (PH) in 2-acetylaminofluorene/PH oval cell proliferation model. Conditional medium (CM) from HSCs were collected to detect their effects on proliferation and the mitogen-activated protein kinase pathway activation of two oval cell lines. We found that CM collected from HSCs at early phase of liver regeneration (4 and 9 days group) contained high levels of hepatocyte growth factor (HGF) and stimulated oval cell proliferation via extracellular signal-regulated kinase and p38 pathway. CM collected from HSCs at terminal phase of liver regeneration (12 and 15 days group) contained high levels of transforming growth factor (TGF)-β1, which suppressed DNA synthesis of oval cells. The shift between these two distinct effects depended on the balance between HGF and TGF-β1 secreted by HSCs. Our study demonstrated that HSCs acted as a positive regulator at the early phase and a negative regulator at the terminal phase of the oval cell-mediated liver regeneration.
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Qiao-dan
authors.initials: QD
authors.lastname: Zhou
authors.forename: Hong-qiang
authors.initials: HQ
authors.lastname: Yang
authors.forename: Hui-fang
authors.initials: HF
authors.lastname: Liang
authors.forename: Bi-xiang
authors.initials: BX
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D015073:2-Acetylaminofluorene; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases