title: Effect of rapamycin on hepatocyte function and proliferation induced by growth factors.
abstract: BACKGROUND
  Rapamycin is a specific inhibitor of the mammalian target of rapamycin (mTOR). The effect of rapamycin on proliferation and cellular function was studied in hepatocytes stimulated by hepatocyte growth factor (HGF) or transforming growth factor-alpha (TGFalpha).
  
  
  RESULTS
  When isolated rat hepatocytes were cultured at low density, the addition of HGF or TGFalpha increased DNA synthesis but did not affect albumin or fibrinogen concentrations in the medium. In contrast, in hepatocytes cultured at high density, the albumin and fibrinogen concentrations, but not DNA synthesis, were increased by HGF or TGFalpha. The HGF- or TGFalpha-induced increase in DNA synthesis and in albumin or fibrinogen concentrations was suppressed by the addition of rapamycin, as well as wortmannin, a phosphatidylinositol-3 kinase inhibitor.
  
  
  CONCLUSIONS
  HGF and TGFalpha stimulate proliferation and function of hepatocytes depending upon the conditions, and rapamycin inhibited these stimulatory effects, possibly by inhibiting the mTOR-dependent signaling pathway.
authors.affiliation: Department of Gastroenterology, Fuculty of Medicine, University of Tokyo, Tokyo, Japan. tomiya-lim@h.u-tokyo.ac.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tomiya
authors.forename: Miho
authors.initials: M
authors.lastname: Yamaoka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takako
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Mikio
authors.initials: M
authors.lastname: Yanase
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tejima
authors.forename: Kayo
authors.initials: K
authors.lastname: Nagashima
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D000418:Albumins / Q000032:analysis / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000418:Albumins; D000730:Androstadienes; D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D016211:Transforming Growth Factor alpha; D017228:Hepatocyte Growth Factor; D005340:Fibrinogen; D011494:Protein Kinases; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000077191:Wortmannin