title: Suppressive effects of iron on TGF-beta1 production by renal proximal tubular epithelial cells.
abstract: BACKGROUND
  TGF-beta1, which is one of the profibrogenic cytokines, is considered essential for both the tubulointerstitial fibrosis found in chronic kidney diseases and the repair of tissue damage in acute renal injury. Iron plays an important part in inflammatory damage since it supplies cytotoxic hydroxyl radicals. The aim of the present study was to examine the direct effects of iron on TGF-beta1 production and the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, by human renal proximal tubular epithelial cells (RPTEC).
  
  
  METHODS
  Using human RPTEC, TGF-beta1 expression was studied by immunohistochemical staining, ELISA and RNase protection assays. 8-OHdG expression was evaluated by immunohistochemical staining.
  
  
  RESULTS
  Ferric iron suppressed both TGF-beta1 secretion and mRNA expression, and enhanced 8-OHdG expression in RPTEC in a dose-dependent manner. Desferrioxamine, an iron chelator, eliminated the suppressive effect of ferric citrate on TGF-beta1 production.
  
  
  CONCLUSIONS
  The results suggest that iron may delay the repair of kidney injury during the acute inflammatory phase via a reduction in TGF-beta1 production by RPTEC. Iron chelation may therefore be a useful strategy in the treatment of inflammatory kidney diseases.
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Nankoku, Japan. horinot@med.kochi-u.ac.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Horino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000208:Acute Disease; D018929:Cell Culture Techniques; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000502:physiology; D005355:Fibrosis / Q000503:physiopathology; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis; D007150:Immunohistochemistry; D007249:Inflammation; D007501:Iron / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology* / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal; D016877:Oxidants / Q000032:analysis; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D016877:Oxidants; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007501:Iron; D003849:Deoxyguanosine