title: Genetic analysis of expression profile involved in retinoid metabolism in non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  The patients with non-alcoholic fatty liver disease (NAFLD) have been reported to be at greater risk for progression to chronic liver disease including liver cirrhosis (LC). To examine the mechanisms for the progression of NAFLD, a genetic analysis of hepatic expression profile in retinoid metabolism in NAFLD was performed since the loss of retinoid signaling is associated with the progression of liver disease via reactive oxygen species (ROS) generation.
  
  
  METHODS
  Fifty-one genes, which are associated with retinoid metabolism and action, were examined in thirty six subjects including 17 patients with simple steatosis, 11 with non-alcoholic steatohepatitis (NASH) and eight controls were examined by real-time reverse transcriptase polymerase chain reaction. Immunohistochemical study was also done by 3 kinds of antibodies.
  
  
  RESULTS
  Higher expression of CRBP1 LRAT, DGT1/2 and CES1 in NAFLD suggests that mutual conversion between retinyl ester and retinal occurs actively. Expression of ADH1/2/3, RDH5/10/11, DHRS3 and RALDH1/3 was increased in NAFLD, suggesting that oxidation process from retinol to all-trans retinoic acid (ATRA) was enhanced. Importantly, greater expression of CYP26A1 indicated that degradation of ATRA was enhanced in NAFLD. Further, expression of SOD1/2, catalase, thioredoxin and uncoupling protein 2 was also enhanced.
  
  
  CONCLUSIONS
  Hyperdynamic state of retinoid metabolism is present in the liver tissues with NAFLD, which may be a putative mechanism by which NAFLD progresses to chronic liver disease including LC.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Yokohama, Japan.
authors.forename: An Afida
authors.initials: AA
authors.lastname: Ashla
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Koich
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Kohei
authors.initials: K
authors.lastname: Shomori
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota