title: Importance of peroxisome proliferator-activated receptor-gamma in hepatic ischemia/reperfusion injury in mice.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcriptional factor belonging to the nuclear receptor superfamily. Recent studies have suggested that PPARgamma regulates inflammatory responses and PPARgamma specific agonists have beneficial effects on several disease conditions in the various organs. However, the precise role of PPARgamma in acute liver injury remains unknown.
  
  
  METHODS
  We investigated the pathophysiological role of PPARgamma and the effect of the selective PPARgamma agonist, pioglitazone, on the hepatic ischemia/reperfusion (I/R) injury.
  
  
  RESULTS
  PPARgamma expression in the liver was upregulated after reperfusion following ischemia. Pioglitazone treatment significantly inhibited hepatic I/R injury as determined by serological and histological analyses. The protective effect was associated with downregulation of the local expression of several potent proinflammatory cytokines, chemokines and adhesion molecules after reperfusion. The neutrophil accumulation was also inhibited by the treatment. Furthermore, the treatment inhibited the induction of apoptosis on hepatocytes. Finally, pioglitazone significantly improved the mouse survival in a lethal model of hepatic I/R injury.
  
  
  CONCLUSIONS
  PPARgamma plays an inhibitory role in hepatic I/R injury and the stimulation by selective agonist has a significant beneficial effect. Thus, PPARgamma may be a new therapeutic target for the protection of the liver against acute injury.
authors.affiliation: Department of Surgery, Nara Medical University, Nara, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Akahori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hamada
authors.forename: Yasue
authors.initials: Y
authors.lastname: Suzaki
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Kuzumoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Nomi
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Enomoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kanehiro
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000473:pathology; D007249:Inflammation / Q000276:immunology; D008107:Liver Diseases / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D009504:Neutrophils / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D000077205:Pioglitazone; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control*; D015996:Survival Rate; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone