Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10766407 | Biochemical and Biophysical Research Communications | 2009 | 6 Pages |
Abstract
Transforming growth factor-β (TGF-β) is known to promote the accumulation of extracellular matrix (ECM) and the development of diabetic nephropathy. Halofuginone, an analog of febrifugine, has been shown to block TGF-β1 signaling and subsequent type I collagen production. Here, the inhibitory effect of halofuginone on diabetic nephropathy was examined. Halofuginone suppressed Smad2 phosphorylation induced by TGF-β1 in cultured mesangial cells. In addition, the expression of TGF-β type 2 receptor decreased by halofuginone. Halofuginone showed an inhibitory effect on type I collagen and fibronectin expression promoted by TGF-β1. An in vivo experiment using db/db mice confirmed the ability of halofuginone to suppress mesangial expansion and fibronectin overexpression in the kidneys. Moreover, an analysis of urinary 8-OHdG level and dihydroethidium fluorescence revealed that halofuginone reduced oxidative stress in the glomerulus of db/db mice. These data indicate that halofuginone prevents ECM deposition and decreases oxidative stress, thereby suppressing the progression of diabetic nephropathy.
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Authors
Seiya Sato, Harukiyo Kawamura, Minoru Takemoto, Yoshiro Maezawa, Masaki Fujimoto, Tatsushi Shimoyama, Masaya Koshizaka, Yuya Tsurutani, Aki Watanabe, Shiro Ueda, Karin Halevi, Yasushi Saito, Koutaro Yokote,