title: Proteomic analysis to display the effect of low doses of erythropoietin on rat liver regeneration.
abstract: OBJECTIVE
  Several groups found different impact of erythropoietin (EPO) on liver regeneration. Both pro-proliferative as well as anti-proliferative and non-proliferative activities have been reported using high dosage of EPO. Systemic administration of high doses of this cytokine is a clinical concern due to risk of thrombosis. Herein, we applied EPO in low dosages and investigated whether it can stimulate liver regeneration after liver resection.
  
  
  METHODS
  Parameters of liver regeneration were assessed 3 days after 70% hepatectomy by means of immunochemistry and proteomics. EPO was given twice in low dosages (200 and 600 IU/kg BW).
  
  
  RESULTS
  We showed that EPO facilitated hepatic regeneration in rats. Enhanced hepatocyte proliferation (Ki67, BrdU-positive cells) was observed in all EPO-treated groups. By performing Differential Proteomic analysis, we identified two proteins which resulted sensitive to EPO treatment after hepatectomy: Peroxiredoxin-1 and glutathione S-transferase Mu 1.
  
  
  CONCLUSIONS
  Based on our results, low doses of rhEPO increase the hepatic regenerative capacity after partial hepatectomy in rats by enhancing hepatocyte proliferation and acting on antioxidant enzymes. Both proteins identified by proteomic analysis have not previously been associated with liver regeneration and will aid in the understanding of EPO's regenerative response having clinical implications to treat liver failure.
authors.affiliation: Department of Cell Technologies and Applied Stem Cell Biology, Biomedical-Biotechnological Center, University Leipzig, Leipzig, Germany. augustinus.bader@bbz.uni-leipzig.de
authors.forename: Augustinus
authors.initials: A
authors.lastname: Bader
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlica
authors.forename: Andrea
authors.initials: A
authors.lastname: Deiwick
authors.forename: Halka
authors.initials: H
authors.lastname: Lotkova
authors.forename: Otto
authors.initials: O
authors.lastname: Kucera
authors.forename: Kai
authors.initials: K
authors.lastname: Darsow
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bartel
authors.forename: Mattes
authors.initials: M
authors.lastname: Schulze
authors.forename: Harald A
authors.initials: HA
authors.lastname: Lange
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Cervinkova
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D008297:Male; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004921:Erythropoietin