title: Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats.
abstract: BACKGROUND
  Recent studies have demonstrated that podocyte injury, which results in proteinuria, leads to tubulointerstitial fibrosis. Although some studies have revealed that vitamin D administration protects renal structure and function in mesangial cell proliferative and/or excessive matrix productive models, the effects of vitamin D on podocyte injury have remained uncertain.
  
  
  METHODS
  In this study, we examined whether administration of active vitamin D (calcitriol) or its analogue, 22-oxacalcitriol (maxacalcitol), is preventative in podocyte injury using the puromycin aminonucleoside nephrosis model with neither mesangial proliferation nor matrix accumulation.
  
  
  RESULTS
  Before the onset of proteinuria, renal 1alpha-hydroxylase and 24-hydroxylase were markedly down-regulated and up-regulated, respectively, leading to impaired vitamin D activation. Thereafter, serum 25-hydroxyvitamin D decreased along with the increased excretion of vitamin D-binding protein in urine. After confirming that podocytes express vitamin D receptor and all retinoid X receptors (RXRs) except RXR-alpha, we found that daily administration of calcitriol or its analogue 22-oxacalcitriol ameliorated the nephrotic state by protecting podocytes, as shown by the reduced staining of desmin (podocyte injury marker) and the upregulation of nephrin and podocin. These data suggest that the impairment of the vitamin D system plays a role in increasing proteinuria in podocyte injury.
  
  
  CONCLUSIONS
  We demonstrated the breakdown of the vitamin D activation system in podocyte injury, and established a preventative role for vitamin D in podocyte injury.
authors.affiliation: 1Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.forename: Kodo
authors.initials: K
authors.lastname: Tomida
authors.forename: Kazunori
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Takabatake
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawada
authors.forename: Takahito
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002120:Calcium Channel Agonists; D012333:RNA, Messenger; D011692:Puromycin Aminonucleoside; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; C051883:maxacalcitol