title: Erythropoietin decreases carbon tetrachloride-induced hepatic fibrosis by inhibiting transforming growth factor-beta.
abstract: BACKGROUND
  In addition to hematopoietic effect, the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities. The purpose of this study was to evaluate the effect of recombinant human erythropoietin (rhEPO) on hepatic fibrosis and hepatic stellate cells (HSCs).
  
  
  METHODS
  Carbon tetrachloride (CCl(4)) induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study. CCl(4) and rhEPO (0, 200 or 1000 U/kg) was injected intraperitoneally in BALB/c mice three times a week for 4 weeks. Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and fibronectin in explanted liver. Immunoblotting of α-SMA, phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO.
  
  
  RESULTS
  Expressions of TGF-β1, α-SMA, and fibronectin were increased in CCl(4) injected mice livers, but significantly attenuated by co-treatment with CCl(4) and rhEPO. Co-treatment of rhEPO markedly suppressed fibrosis in Masson's trichrome compared with treatment of only CCl(4). TGF-β1 increased phosphorylated α-SMA, Smad-2 expressions in HSCs, which were decreased by rhEPO co-treatment.
  
  
  CONCLUSIONS
  Treatment of rhEPO effectively suppressed fibrosis in CCl(4)-induced liver fibrosis mice models. Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.
authors.affiliation: Department of Internal Medicine, Liver Research Institute, Graduate School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.forename: Young Oh
authors.initials: YO
authors.lastname: Kweon
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005353:Fibronectins / Q000032:analysis; D055166:Hepatic Stellate Cells / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D005353:Fibronectins; D011994:Recombinant Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D004921:Erythropoietin; D002251:Carbon Tetrachloride