Halofuginone prevents extracellular matrix deposition in diabetic nephropathy

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• 作者：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 Y
• 关键词：Halofuginone ; Diabetic nephropathy ; TGF-β ; Type I collagen ; Fibronectin ; TGF-β ; type 2 receptor ; Mesangial cell ; Oxidative stress
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：6 February 2009
• 年：2009
• 卷：379
• 期：2
• 页码：411-416
• 全文大小：470 K

文摘

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.