MISC

2009年8月

Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats

NEPHROLOGY DIALYSIS TRANSPLANTATION
  • Isao Matsui
  • Takayuki Hamano
  • Kodo Tomida
  • Kazunori Inoue
  • Yoshitsugu Takabatake
  • Yasuyuki Nagasawa
  • Noritaka Kawada
  • Takahito Ito
  • Hiroshi Kawachi
  • Hiromi Rakugi
  • Enyu Imai
  • Yoshitaka Isaka
  • 全て表示

24
8
開始ページ
2354
終了ページ
2361
記述言語
英語
掲載種別
DOI
10.1093/ndt/gfp117
出版者・発行元
OXFORD UNIV PRESS

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 1 alpha-hydroxylase and 24-hydroxylase were markedly downregulated 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.

リンク情報
DOI
https://doi.org/10.1093/ndt/gfp117
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000268115400012&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/ndt/gfp117
  • ISSN : 0931-0509
  • Web of Science ID : WOS:000268115400012

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