書誌事項
- タイトル別名
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- TGF-β1/Smad3 Signaling in Renal Tubulointerstitial Fibrosis
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Transforming growth factor (TGF) -β constitutes a superf amily of multifunctional cytokines that regulate a variety of cellular responses including cell proliferation, apoptosis and extracellular matrix deposition. TGF-β1 is reportedly upregulated in tubulointerstitial fibrosis as characterized by epithelilal-mesenchymal transition (EMT) in the renal tubules and excessive accumulation of extracellular matrix with monocyte influx. Here we show that mice lacking Smad3, a key mediator of TGF-β signaling, are protected against tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) . Primary culture of renal tubular epithelial cells from Smad3-null or wild-type mice demonstrated that TGF-β1-induced EMT of the renal tubules and autoinduction of TGF-β1 require Smad3 signaling. Cyclic stretching of cultured renal tubular epithelial cells that mimics distention of the renal tubules by UUO induces EMT and upregulation of TGF-βl in a Smad3-dependent manner. Exogenous bone marrow monocytes accelerate EMT of the cultured renal tubular epithelial cells and renal tubules in the obstructed kidney by UUO dependent on TGF-β1/Smad3 signaling. These data indicate that the Smad3 pathway is essential for the pathogenesis of renal tubulointerstitial fibrosis and suggests that small-molecule inhibitors of this pathway may have clinical application in the treatment of fibroinflammatory nephropathy.
収録刊行物
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- 日本疾患モデル学会記録
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日本疾患モデル学会記録 21 12-16, 2005
公益社団法人 日本実験動物学会
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詳細情報 詳細情報について
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- CRID
- 1390282679350109696
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- NII論文ID
- 130000760625
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- ISSN
- 18844197
- 09188991
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
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- CiNii Articles
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- 使用不可