title: [The role of glycogen synthase kinase-3 beta in the pathogenesis of liver ischemia reperfusion injury].
abstract: OBJECTIVE
  To investigate the role of the key intracellular signaling molecule glycogen synthase kinase-3 beta in the mechanism of liver ischemia reperfusion (IR).
  
  
  METHODS
  C57BL/6 mice were subjected to 90 min warm liver cephalad lobe ischemia, followed by various length of reperfusion. Experiment groups included sham control group, liver IRI model group and glycogen synthase kinase-3 beta inhibitor-treated group (SB216763 in DMSO, 25 g/kg, i.p, 2 hour prior to the onset of liver ischemia). The expression of glycogen synthase kinase-3 beta protein was analysed by Western blotting. The serum ALT levels were determined to reflect the function of liver. The affected liver lobes were harvested for histology analysis. The inflammatory gene expression was detected by Quantitative PCR.
  
  
  RESULTS
  By western blot analysis, we found that ischemia itself activated glycogen synthase kinase-3 beta by a significant decrease of its phosphorylation. Glycogen synthase kinase-3 beta inhibitor SB216763-pretreatment ameliorated the liver damages significantly as compared to the controls (sALT: 2046+/-513 U/L vs 5809+/-1689 U/L, P = 0.0153), and suppressed the gene expressions of IL-12, TNFa, IL-1b and IL-6.
  
  
  CONCLUSIONS
  This study demonstrated that the ischemia process modulated liver innate immune activation via a GSK-3-dependent mechanism which favored the development of a pro-inflammation response and lead to liver tissue damages. GSK-3b may be a new therapeutic target to ameliorate liver IRI in transplant patients.
authors.affiliation: Beijing Institute of Liver Diseases, Beijing 100069, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Zheng-fu
authors.initials: ZF
authors.lastname: Piao
authors.forename: Su-jun
authors.initials: SJ
authors.lastname: Zheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: Wu
authors.forename: Zhong-ping
authors.initials: ZP
authors.lastname: Duan
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3