MISC

2001年5月

A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis

AMERICAN JOURNAL OF PATHOLOGY
  • K Makibayashi
  • M Tatematsu
  • M Hirata
  • N Fukushima
  • K Kusano
  • S Ohashi
  • H Abe
  • K Kuze
  • A Fukatsu
  • T Kita
  • T Doi
  • 全て表示

158
5
開始ページ
1733
終了ページ
1741
記述言語
英語
掲載種別
出版者・発行元
AMER SOC INVESTIGATIVE PATHOLOGY, INC

OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong inhibitory effects on mesangial cell proliferation in vitro. In the present study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis. Both OCT and 1,25(OH)(2)D-3 significantly inhibited mesangial cell proliferation, the degree of glomerulosclerosis, and albuminuria at day 8 compared to the disease control group. The OCT-treated group showed normal calcium levels but the 1,25(OH)(2)D-3-treated group showed higher levels. The disease control group showed a marked increase of type I and type IV collagens, and alpha -smooth muscle actin (alpha -SMA) compared to the normal group. The treatment of OCT or 1,25(OH)(2)D-3 significantly reduced the expression of these proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly higher levels of type I and type IV collagens, and alpha -SMA at day 8 compared to normal rats. Treatment with OCT Or 1,25(OH)(2)D-3 inhibited the mRNA expressions of type I and type IV collagens, as well, as that of alpha -SMA. These data demonstrate that OCT inhibits mesangial cell proliferation and extracellular matrix expansion with a low calcemic activity. Disease control rats showed significantly increased levels of transforming growth factor-alpha protein in the glomeruli, but treatment with OCT or 1,25(OH)(2)D-3 markedly reduced this expression. The levels of mRNA in glomeruli were also consistent with these protein levels. Therefore, the suppressive effect of OCT may be mediated by inhibition of transforming growth factor-alpha. The present results suggest that OCT has potential for use in therapeutic strategy for the treatment of glomerulonephritis without inducing hypercalcemia.

リンク情報
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000168549000021&DestApp=WOS_CPL
ID情報
  • ISSN : 0002-9440
  • Web of Science ID : WOS:000168549000021

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