title: Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.
abstract: BACKGROUND
  Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury.
  
  
  METHODS
  CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death.
  
  
  RESULTS
  Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3).
  
  
  CONCLUSIONS
  rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Kyung Ohk
authors.initials: KO
authors.lastname: Ahn
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: In Sung
authors.initials: IS
authors.lastname: Moon
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000188:drug therapy*; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D004921:Erythropoietin; D016572:Cyclosporine; D002097:C-Reactive Protein