論文

査読有り
2007年3月

Enhanced TGF-beta/Smad signaling in the early stage of diabetic nephropathy is independent of the AT1a receptor.

Clinical and experimental nephrology
  • Yuko Okazaki
  • Yasushi Yamasaki
  • Haruhito A Uchida
  • Kazunori Okamoto
  • Minoru Satoh
  • Keisuke Maruyama
  • Yohei Maeshima
  • Hitoshi Sugiyama
  • Takeshi Sugaya
  • Naoki Kashihara
  • Hirofumi Makino
  • 全て表示

11
1
開始ページ
77
終了ページ
87
記述言語
英語
掲載種別
研究論文(学術雑誌)

BACKGROUND: Angiotensin II (AII) and transforming growth factor-beta (TGF-beta) are closely involved in the pathogenesis of diabetic nephropathy (DN). AII is known to induce TGF-beta production in resident renal cells, including glomerular mesangial cells and tubular epithelial cells. TGF-beta receptor types I and II (TGF-betaRI, II) are up-regulated in the diabetic kidney. The aim of this study was to clarify the role of AII in the regulation of the TGF-beta system in the early stage of DN using AII type1a receptor-deficient(AT1a(-/-)) mice. METHODS: We investigated the expression of TGF-beta1, TGF-betaRI, II, and Smad signaling in AT1a(-/-) mice with streptozotocin (STZ)-induced DN. Mice were killed 10 and 20 days after the induction of hyperglycemia. The expression of TGF-beta receptors was analyzed by immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR). TGF-beta-specific Smad signaling was analyzed by electrophoretic mobility shift assay and Western blotting. RESULTS: The expression of both TGF-betaRI and RII was up-regulated in the glomerular tufts and vasculature in diabetic AT1a(+/+) mice kidney by immunohistochemistry. RT-PCR revealed that mRNAs for TGF-betaRI and RII were also up-regulated. Smad2 and 4 protein levels were reduced in the renal cortex after the induction of diabetes, with an increase of Smad 3/4 complex in the nucleus. The expression of TGF-beta receptors increased in both diabetic AT1a(-/-) and AT1a(+/+) mice. Smad signaling in AT1a(-/-) mice was also enhanced. CONCLUSIONS: Our results suggest that the complete blockade of the AT1a-mediated pathway has a minimal effect on the enhanced TGF-beta/Smad signaling in the early stage of DN, at least in the AT1a(-/-) model.

リンク情報
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17385003
ID情報
  • ISSN : 1342-1751
  • PubMed ID : 17385003

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