title: Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation.
abstract: OBJECTIVE
  To clarify the molecular mechanism of polyenylphosphatidylcholine (PPC), we examined the involvement of reactive oxygen species (ROS) and NADPH oxidase 4 (Nox4) in human hepatic stellate cells (HSCs).
  
  
  METHODS
  Using human LX-2 HSC cells, we examined the effects of PPC on expression of α-smooth muscle actin (α-SMA) and collagen 1, generation of ROS, Nox4 expression, p38 activation and cell proliferation, induced by transforming growth factor β1 (TGFβ1).
  
  
  RESULTS
  PPC suppressed ROS which are induced by TGFβ1, phosphorylation of p38MAPK, and expression levels of α-SMA and collagen 1 in a dose-dependent manner. Higher concentrations of PPC also suppressed Nox4 levels.
  
  
  CONCLUSIONS
  These results suggest that ROS and Nox4 induced by TGFβ1 are the therapeutic targets of PPC in the suppression of human hepatic stellate cell activation.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, 683-8504, Japan.
authors.forename: Remina
authors.initials: R
authors.lastname: Ikeda
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ishii
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Junya
authors.initials: J
authors.lastname: Azumi
authors.forename: Yuta
authors.initials: Y
authors.lastname: Arakaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasui
authors.forename: Shizuka
authors.initials: S
authors.lastname: Matsuura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Matsumi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kono
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizuta
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.forename: Hironaka
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
mesh_terms: D002460:Cell Line; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D010713:Phosphatidylcholines; D020011:Protective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; C005152:lipostabil; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human