title: Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease.
abstract: Iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD). Renal fibrosis is a final common feature that contributes to the progression of CKD; however, little is known about the association between renal iron accumulation and renal interstitial fibrosis in CKD. Here we investigate the effects of iron chelation on renal interstitial fibrosis in a rat model of CKD. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. At 8 weeks after operation, 5/6 nephrectomized rats were administered an oral iron chelator, deferasirox (DFX), in chow for 8 weeks. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats exhibited hypertension, glomerulosclerosis and renal interstitial fibrosis. Iron chelation with DFX did not change hypertension and glomerulosclerosis; however, renal interstitial fibrosis was attenuated in CKD rats. Consistent with these findings, renal gene expression of collagen type III and transforming growth factor-β was increased in CKD rats compared with the controls, while iron chelation suppressed these increments. In addition, a decrease in vimentin along an increase in E-cadherin in renal gene expression was observed in CKD rats with iron chelation. CKD rats also showed increased CD68-positive cells in the kidney, whereas its increase was attenuated by iron deprivation. Similarly, increased renal gene expression of CD68, tumor necrosis factor-α and monocyte chemoattractant protein-1 was suppressed in CKD rats with iron chelation. Renal iron accumulation seems to be associated with renal interstitial fibrosis in a rat model of CKD.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Fujii
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Oboshi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morisawa
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure; D000077588:Deferasirox; D005355:Fibrosis / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009392:Nephrectomy; D009395:Nephritis, Interstitial / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox