論文

査読有り
2006年2月

A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice

DIABETES
  • R Inagi
  • ,
  • Y Yamamoto
  • ,
  • M Nangaku
  • ,
  • N Usuda
  • ,
  • H Okamato
  • ,
  • K Kurokawa
  • ,
  • CV de Strihou
  • ,
  • H Yamamoto
  • ,
  • T Miyata

55
2
開始ページ
356
終了ページ
366
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.2337/diabetes.55.02.06.db05-0702
出版者・発行元
AMER DIABETES ASSOC

Many factors are involved in the pathogenesis of diabetic nephropathy. A single gene abnormality may be prerequisite but insufficient to the disease to manifest. It is therefore only when a second or sometimes a third damage is associated that the consequences of pathogenic phenotypes become evident. We generated the triple transgenic mice overexpressing megsin (a novel glomerular-specific serpin), a receptor for advanced glycation end products (RAGE), and inducible nitric oxide synthase (iNOS). Compared with the single- or two-gene transgenic mice, the triple transgenic mice developed, at an early age (16 weeks), severe albuminuria and renal damage with all of the characteristics of human diabetic nephropathy (i.e. glomerular hypertrophy, diffuse mesangial expansion, Inflammatory cell infiltration, and interstitial fibrosis). Interestingly, 30-40% of glomeruli exhibit nodule-like lesions. Oxidative and carbonyl stress makers (pentosidine, N-carboxymethyllysine, and 8-hydroxy-deoxyguanosine) were significantly higher in the triple transgenic mice. The iNOS transgenic mice have a diabetes phenotype, the renal consequences of which are moot, and the superimposition of RAGE leads to more conspicuous manifestations. By additional overexpression of megsin, a gene known to be involved in mesangial proliferation and expansion, these local consequences become dramatically manifest and approximate those observed in human pathology. This multiple hit approach is of interest in consideration of the sequential events during development of diabetic nephropathy.

リンク情報
DOI
https://doi.org/10.2337/diabetes.55.02.06.db05-0702
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000235178400013&DestApp=WOS_CPL
ID情報
  • DOI : 10.2337/diabetes.55.02.06.db05-0702
  • ISSN : 0012-1797
  • Web of Science ID : WOS:000235178400013

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