Document Detail


Halofuginone prevents extracellular matrix deposition in diabetic nephropathy.
MedLine Citation:
PMID:  19114027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transforming growth factor-beta (TGF-beta) 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-beta(1) 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-beta(1) in cultured mesangial cells. In addition, the expression of TGF-beta type 2 receptor decreased by halofuginone. Halofuginone showed an inhibitory effect on type I collagen and fibronectin expression promoted by TGF-beta(1). 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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  379     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-21     Completed Date:  2009-02-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411-6     Citation Subset:  IM    
Affiliation:
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Collagen Type I / antagonists & inhibitors,  metabolism
Diabetic Nephropathies / metabolism*,  pathology*
Extracellular Matrix / drug effects*,  pathology*
Fibronectins / antagonists & inhibitors,  metabolism
Mesangial Cells / drug effects,  metabolism,  pathology
Mice
Mice, Inbred Strains
Oxidative Stress / drug effects
Piperidines / pharmacology*
Quinazolinones / pharmacology*
Rats
Smad2 Protein / metabolism
Transforming Growth Factor beta / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Collagen Type I; 0/Fibronectins; 0/Piperidines; 0/Quinazolinones; 0/Smad2 Protein; 0/Transforming Growth Factor beta; 17395-31-2/halofuginone

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