Suppressive effects of iron on TGF-beta1 production by renal proximal tubular epithelial cells.
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.
Horino
Taro
T
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Nankoku, Japan. horinot@med.kochi-u.ac.jp
Ito
Hiroyuki
H
Yamaguchi
Takuya
T
Furihata
Mutsuo
M
Hashimoto
Kozo
K
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
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