title: Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells.
abstract: BACKGROUND
  Activin A, an important member of transforming growth factor-β superfamily, is reported to inhibit proliferation of mature hepatocyte. However, the effect of activin A on growth of hepatic progenitor cells is not fully understood. To that end, we attempted to evaluate the potential role of activin A in the regulation of hepatic progenitor cell proliferation.
  
  
  RESULTS
  Using the 2-acetaminofluorene/partial hepatectomy model, activin A expression decreased immediately after partial hepatectomy and then increased from the 9th to 15th day post surgery, which is associated with the attenuation of oval cell proliferation. Activin A inhibited oval cell line LE6 growth via activating the SMAD signaling pathway, which manifested as the phosphorylation of SMAD2/3, the inhibition of Rb phosphorylation, the suppression of cyclinD1 and cyclinE, and the promotion of p21WAF1/Cip1 and p15INK4B expression. Treatment with activin A antagonist follistatin or blocking SMAD signaling could diminish the anti-proliferative effect of activin A. By contrast, inhibition of the MAPK pathway did not contribute to this effect. Antagonizing activin A activity by follistatin administration enhanced oval cell proliferation in the 2-acetylaminofluorene/partial hepatectomy model.
  
  
  CONCLUSIONS
  Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hui-fang
authors.initials: HF
authors.lastname: Liang
authors.forename: Qiao-fan
authors.initials: QF
authors.lastname: Zhou
authors.forename: Ze-yang
authors.initials: ZY
authors.lastname: Ding
authors.forename: Hong-qiang
authors.initials: HQ
authors.lastname: Yang
authors.forename: Wei-bo
authors.initials: WB
authors.lastname: Liu
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Wu
authors.forename: Quan
authors.initials: Q
authors.lastname: Man
authors.forename: Bi-xiang
authors.initials: BX
authors.lastname: Zhang
authors.affiliation: Hepatic surgery centre, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. chenxp@medmail.com.cn.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D038681:Follistatin / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: C493958:Cdkn1a protein, rat; D019927:Cyclin E; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21; D038681:Follistatin; D051785:Smad Proteins; C422405:activin A; D028341:Activins; D019938:Cyclin D1