Ischemia-reperfusion of rat liver modulates hepcidin in vivo expression

Liver Transpl. 2005 Jul;11(7):800-806. doi: 10.1002/lt.20436.


The recently identified acute-phase response antimicrobial peptide hepcidin has been postulated to maintain iron homeostasis by modulating iron absorption at both the intestinal and macrophage levels. Hepcidin has also been reported to be responsible for anemia associated with chronic inflammatory diseases, and in anemia in patients with hepatic adenomas. Since Kupffer cells are known to be the primary contributor to early-phase ischemia-reperfusion injury in the liver and iron is known to modulate Kupffer cell production of proinflammatory cytokine and reactive oxygen species, we investigated hepcidin in vivo expression in the well-established rat partial-liver ischemia-reperfusion model. We found that both liver ischemia alone and liver ischemia-reperfusion significantly induced serum and liver hepcidin levels. Furthermore, currently proposed mediators of in vivo hepcidin expression, such as interleukin-6, signal transducers and activators of transcription-family transducers, and CCAAT/enhancing binding protein-alpha do not appear to modulate hepcidin expression in the liver ischemia-reperfusion acute inflammatory model. In this study we report the first in vivo evidence of liver ischemia and liver ischemia-reperfusion modulation of hepcidin expression. In conclusion, in the well-characterized liver ischemia-reperfusion model of acute inflammation, mechanism(s) other than interleukin-6 signal transduction via signal transducers and activators of transcription-3 may be responsible for hepcidin induction.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / blood
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Aspartate Aminotransferases / blood
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Hepcidins
  • Immunohistochemistry
  • Interleukin-6 / blood
  • Iron / blood
  • L-Lactate Dehydrogenase / blood
  • Liver / blood supply*
  • Liver / metabolism*
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / metabolism*
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Severity of Illness Index


  • Antimicrobial Cationic Peptides
  • CCAAT-Enhancer-Binding Protein-alpha
  • Hamp protein, rat
  • Hepcidins
  • Interleukin-6
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, rat
  • Stat3 protein, rat
  • Iron
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases